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™ Oncology specialty topic page highlights the latest clinical care news related to the development of cell therapies, gene therapies, and engineered and regenerative medicines for various cancers. It also houses video interviews with key opinion leaders in the field of oncology speaking to the related FDA actions, clinical guideline updates, and clinical trial findings in the field of gene and cell therapy for oncologic diseases.

In Episode 5 of ImmunoLogic, Michael T. Lotze, MD, discussed the evolution and future of tumor infiltrating lymphocyte (TIL) therapies.

ImmunoLogic, Episode 5: "Tumor Infiltrating Lymphocytes" With Michael T. Lotze, MD

We're excited to introduce another episode of the 

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Fraietta is often joined by cohost 

 a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

a professor of surgery, immunology, and bioengineering at the University of Pittsburgh, about his work on tumor infiltrating lymphoctye (TIL) therapy. Fraietta and Lotze covered topics including the history of TIL research, the potential of TIL therapy in different tumor types, Lotze and his colleagues' new reciprocal learning model hypothesis, and concluded with some philosophical reflections on cancer research.

 is tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. This podcast is an essential resource for those driving the future of immunotherapy.

Interested in co-hosting an episode or being a guest? Have feedback to share? 

If you'd like to get in touch to talk about the show, contact our editorial director, Matt Hoffman: 

Podcasts

In Episode 4 of ImmunoLogic, Caroline Diorio, MD, FRCPC, FAAP, discussed her research on adverse events associated with CAR-T.

 ImmunoLogic, Episode 4: "Inflammatory Storms and Gentle Balances" With Caroline Diorio, MD, FRCPC, FAAP

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Fraietta is joined by cohost 

an attending physician at the Cancer Center at Children's Hospital of Philadelphia, about her research into inflammatory toxicities in cell therapy. Diorio, Fraietta, and Minehart covered topics including predicting and managing toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), the need for rigorous research to understand the underlying biology of these toxicities, the importance of transparency in manufacturing processes, and the potential for decoupling potency from toxicity.

In Episode 4 of ImmunoLogic, Caroline Diorio, MD, FRCPC, FAAP, discussed her research on adverse events associated with cell therapy.

ImmunoLogic, Episode 4: "Inflammatory Storms and Gentle Balances: Navigating Toxicities in Immunotherapies" With Caroline Diorio, MD, FRCPC, FAAP

In Episode 3 of ImmunoLogic, Marcela Maus, MD, PhD, discussed her research on CAR-T for treating glioblastoma.

ImmunoLogic, Episode 3: "Breaking the Brain’s Barrier: CAR T Cells Take on Glioblastoma" With Marcela Maus, MD, PhD

the director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center, about her research into the use of chimeric antigen receptor T-cell (CAR-T) therapy to treat glioblastoma. Maus, Fraietta, and Minehart covered topics including challenges and insights from early clinical trials, innovations and clinical results, antigen expression and the possibility of readministration, as well as the autologous versus allogeneic debate.

ImmunoLogic, Episode 3: "Breaking the Brain’s Barrier: CAR T-Cells Take on Glioblastoma" With Marcela Maus, MD, PhD

In Episode 2 of ImmunoLogic, Bruce Levine, PhD, discussed the current the risk-benefit-ratio for CAR-T therapy.

ImmunoLogic, Episode 2: "Charting New Frontiers in CAR T-Cell Safety" With Bruce Levine, PhD

, a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

 the Barbara and Edward Netter Professor in Cancer Gene Therapy at the Perelman School of Medicine at the University of Pennsylvania, about the black box warnings for secondary malignancies that were issued by the FDA with regard to the autologous chimeric antigen receptor T-cell (CAR-T) therapies approved by the agency, and the implications of the findings that informed these warnings for the risk-benefit ratio of these therapies. Levine, Fraietta, and Minehart covered topics including risk and informed consent, genetic modification as it relates to safety, epitope spreading and T-cell stimulation, and the importance of the National Institutes of Health (NIH) to CAR T-cell research.

In Episode 1 of ImmunoLogic, Stephen J. Schuster, MD, discussed the potential of treating lymphoma without chemotherapy.

ImmunoLogic, Episode 1: "Chemo-Free Lymphoma? Seriously?" With Stephen J. Schuster, MD

, a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will become a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

, the director of the Lymphoma Program at Penn Medicine, about the changing role of chemotherapy in lymphoma treatment, and the potential for its elimination. Schuster covered topics including trials for chimeric antigen receptor T-cell (CAR-T) therapy without lymphodepletion, using AI to predict CAR-T treatment outcomes, the importance of T-cell fitness, and the role of persistence in CAR-T success.

Joseph Fraietta, PhD, previews his new podcast, ImmunoLogic

ImmunoLogic Episode 0

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania! Our hope is that this show will become a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions.

In this short preview episode, Fraietta outlines the podcast’s mission to scrutinize the critical milestones shaping immunotherapy today and discuss how episodes will analyze the journey from bench to bedside—focusing on the real-world implementation of clinical data and the impact of regulatory achievements on patient outcomes. Topics will include discussions on chimeric antigen receptor (CAR) T-cell therapies, tumor-infiltrating lymphocyte (TIL)-based approaches, antibody-driven treatments, and the latest advances in gene editing technologies such as CRISPR, with a goal of expanding the conversation outside of the field of oncology.

 will be tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. With its first full episode launching in early 2025, this podcast promises to be an essential resource for those driving the future of immunotherapy.

Hosted by Joseph Fraietta, PhD, ImmunoLogic will be tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility.

CGTLive® Presents: ImmunoLogic, A Video Podcast With Joseph Fraietta, PhD

Catch up on the latest news, breakthroughs, and announcements from biotechnology companies making advancements in cell and gene therapies. 

Around the Helix: Cell and Gene Therapy Company Updates – July 30, 2025

Review top news and interview highlights from the week ending July 25, 2025.

CGTLive®’s Weekly Rewind – July 25, 2025

The therapy was approved based on findings of the pivotal phase 1b/2 FELIX clinical trial.

European Commission Approves Obe-Cel for Adults With R/R B-Cell Precursor Acute Lymphoblastic Leukemia

Around the Helix: Cell and Gene Therapy Company Updates – July 23, 2025

Review top news and interview highlights from the week ending July 18, 2025.

CGTLive®’s Weekly Rewind – July 18, 2025

This video originally appeared on our sister site,

The professor in the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope discussed unanswered questions with regard to DLBCL treatment sequencing.

Alexey Danilov, MD, PhD, on CAR-T and Bispecific Antibody Sequencing for DLBCL

"In terms of sequencing, there is now an emerging question of whether we should be using bispecifics or CAR T-cells first. Some of this will be driven by logistical issues, some will be driven by whether there is easy accessibility to a tertiary care center that can [administer] CAR T-cell therapy, and some will be driven by patient comorbidities, cost, and other factors."

A number of important considerations exist for sequencing of treatment in patients with diffuse large B-cell lymphoma (DLBCL), as do unanswered questions. In an interview with 

®, Alexey Danilov, MD, PhD, the Marianne and Gerhard Pinkus Professor of Early Clinical Therapeutics, medical director of the Early Phase Therapeutics Program for the Systems Clinical Trials Office, codirector of the Toni Stephenson Lymphoma Center, and a professor in the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California, discussed these topics.

the publication of a consensus manuscript

 looking at therapeutic developments and unmet needs in mantle cell lymphoma, DLBCL, and chronic lymphocytic leukemia.

Danilov pointed out that because multiple highly active therapies, including chimeric antigen receptor (CAR) T-cell therapies, bispecific antibodies, and CD19-directed agents, are now available, optimizing the sequencing of treatment in patients with relapsed/refractory DLBCL has become complex. Whether bispecific antibodies should be administered prior to CAR T-cell therapy or vice versa is now a question of central importance. Danilov stressed that decisions regarding sequencing will likely be affected by a number of factors, such as logistical constraints related to CAR T-cell therapy administration, nearness to specialized treatment centers, comorbidities, and cost factors.

Emerging data suggest bidirectional efficacy between these modalities. Bispecific antibodies, which predominantly target CD20, appear to retain activity following disease progression on CAR T-cell therapy. Conversely, some patients with DLBCL who experience disease progression on bispecific antibodies may still respond to CAR T-cell therapy, contingent upon continued antigen expression. This has important implications for sequencing choices, particularly as bispecific antibodies become more integrated into earlier lines of therapy.

Danilov noted that CAR T-cell therapies have already displaced autologous stem cell transplantation in certain clinical scenarios, such as in patients with primary refractory disease or those who experience relapse within 12 months of frontline chemoimmunotherapy. However, in later lines of therapy, data are growing in support of both CAR T-cell therapy and bispecific antibodies. As a result, optimal sequencing remains undefined, and future comparative and real-world evidence will be critical in shaping the future standard of care.

Videos

Canonical

Alexey Danilov, MD, PhD, on CAR T and Bispecific Antibody Sequencing for DLBCL

The associate professor and the lymphoma stream lead at St Vincent’s Hospital, discussed data from a phase 1b trial for the CD19/CD20–directed bispecific CAR-T.

Matthew Ku, MBBS, FRACP, RACP, FRCPA/RCPA, PhD, on CAR-T Therapy JNJ-90014496's Safety Profile in R/R LBCL

"Overall, only 7 patients, or 28% of the recommended phase 2 dose group, reported a serious treatment emergent adverse event."

Johnson & Johnson’s JNJ-90014496, a CD19 and CD20-directed bispecific chimeric antigen receptor (CAR) T-cell therapy, is currently being evaluated for the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL) in a phase 1b clinical trial (NCT05421663). At 

the European Hematology Association (EHA) 2025 Congress

, held June 12 to 15, both virtually and in Milan, Italy, data from this trial were presented.

, interviewed Matthew Ku, MBBS, FRACP, RACP, FRCPA/RCPA, PhD, an associate professor and the lymphoma stream lead at St Vincent’s Hospital, about the findings during the conference. Ku went over the highlights of the safety and efficacy results presented.

Click here to view more coverage of EHA's 2025 Congress.

Matthew Ku, MBBS, PhD, FRACP, RACP, FRCPA/RCPA, on CAR T-Cell Therapy JNJ-90014496's Safety Profile in R/R LBCL

The associate professor of medicine at Stanford University School of Medicine discussed safety and efficacy data from a study presented at EHA's 2025 congress.

Saurabh Dahiya, MD, FACP, on CAR-T KITE-363's Safety Profile in R/R B-Cell Lymphoma

"At the highest dose level in CAR naive patients, we observed an objective overall response rate of 87% and a complete remission rate of 78%."

Kite's KITE-363, a dual CD19 and CD20-directed chimeric antigen receptor (CAR) T-cell therapy, is currently being evaluated for the treatment of relapsed/refractory (r/r) B-cell lymphoma in a phase 1 clinical trial (NCT04989803). Data from this trial were presented at 

, held June 12 to 15, both virtually and in Milan, Italy.

, interviewed Saurabh Dahiya, MD, FACP, an associate professor of medicine at Stanford University School of Medicine and the clinical director of cancer cell therapy in the Division of Blood and Marrow Transplantation and Cell Therapy at Stanford Medicine, about the findings. Dahiya went over the safety profile of the CAR-T in the trial and also touched on the efficacy results.

This is the second part of an interview with Shahzad Raza, MD. For the first part, 

The hematologist/oncologist at the Cleveland Clinic discussed next steps after early promising results were presented at ASCO’s 2025 meeting.

Shahzad Raza, MD, on Future Plans for CAR-T NXC-201 in R/R Light Chain Amyloidosis

“This is very different than continuing to bring patients to the clinic every week do therapy. A treatment holiday—freedom from more treatments —at least for our timeline, I think would be an important point for these patients. I think the future studies should focus on treatment holidays...”

Immix Biopharma and its subsidiary Nexcella are currently developing NXC-201, an investigational autologous BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy, for the treatment of relapsed/refractory (r/r) light chain (AL) amyloidosis. Notably, early data from the phase 1b/2 NEXICART-2 clinical trial (NCT06097832) evaluating the therapy in the United States were recently presented at 

the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting

, held May 30 to June 3, in Chicago, Illinois.

, spoke with Shahzad Raza, MD, a hematologist/oncologist at the Cleveland Clinic who coauthored the study presented at ASCO, about 

. Afterwards, Raza was asked about future plans for evaluating the CAR-T product in AL amyloidosis and unanswered questions and challenges that still need to be addressed. Raza emphasized that while patients with advanced cardiac amyloidosis (stage 3b) were excluded from the current trial, future studies should explore its use in this high-risk group if safety and efficacy continue to hold. Raza stressed the urgent need for effective second-line treatments and suggested offering CAR-T therapy earlier in the disease course. He highlighted the potential for “treatment holidays,” where patients could avoid continuous therapies after receiving CAR-T, which could improve quality of life.

Raza also spoke about challenges in patient eligibility for treatment, emphasizing the importance of being free from active infections and other disease. He then mentioned his excitement about another presentation at ASCO, which focused on the use of teclistamab, a Bispecific T-cell engager (BiTE), for AL amyloidosis. He spoke about how teclistamab and CAR-T may allow for patients to have multiple treatment options for r/r AL amyloidosis in the future.

Click here to view more coverage of ASCO's 2025 Meeting.

REFERENCE
1. Landau H. Safety and efficacy data from Nexicart-2, the first US trial of CAR-T in R/R light chain (AL) amyloidosis, NXC-201. Presented at the 2025 ASCO Annual Meeting, held May 30 to June 3, in Chicago, Illinois. Abstract #7508

Shahzad Raza, MD, on Future Plans for CAR T-Cell Therapy NXC-201 in R/R Light Chain Amyloidosis

The associate professor of medicine–hematology and clinical director of lymphoma services at the University of Colorado discussed the implications of a large scale analysis of liso-cel recipients.

Manali Kamdar, MD, on Lowering Barriers to Access for Liso-Cel Based on New Data

“I think this really calls for a concerted effort around making sure that this data is out there so that the regulatory bodies can review it and further optimize the requirement around the 4 week window and hopefully shorten it for our patients to less than at least 2 to 2.5 weeks so that we not only allow them to return home, but also make sure that the safety is not compromised.”

Bristol Myers Squibb's lisocabtagene maraleucel (liso-cel, marketed as Breyanzi), an FDA-approved chimeric antigen receptor (CAR) T-cell therapy, has provided a transformative new treatment option for patients with several hematologic malignancy indications in recent years. Although, the treatment does carry a risk of potentially serious adverse events (AEs), especially cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and as such patients receiving liso-cel are required to stay within 30 miles of their academic treating center for a mandated period of 4 weeks. This regulation can pose barriers to access to some patients for logistical and socioeconomic reasons.

Notably, Manali Kamdar, MD, the associate professor of medicine–hematology and clinical director of lymphoma services at the University of Colorado, presented data from an analysis of more than 1,500 patients treated with liso-cel across clinical trials and the real world, at 

, held May 30 to June 3, in Chicago, Illinois. In an interview with 

, Kamdar went over the key findings of this analysis, which included data regarding the incidence, timing, and necessary level of management for AEs. She shared her view that based on these findings, it may be possible to provide patients with personalized tailoring of their monitoring requirements after treatment, thus potentially reducing the amount of time that patients need to remain at their treating center.

REFERENCE
1. Kamdar M. Optimizing post–chimeric antigen receptor (CAR) T cell monitoring: Evidence across lisocabtagene maraleucel (liso-cel) pivotal clinical trials and real-world experience. Presented at the 2025 ASCO Annual Meeting, held May 30 to June 3, in Chicago, Illinois. Abstract #7026

The hematologist/oncologist at the Cleveland Clinic discussed early results from a clinical trial evaluating the BCMA-directed CAR-T therapy

Shahzad Raza, MD, on Evaluating CAR-T NXC-201 in R/R Light Chain Amyloidosis

“So far, the data is quite promising to share that this is very safe... I'm hoping that by the next 6 months, we will have much more mature data, more patients enrolled... The phase 1b and phase 2a is quite exciting. This data does show it's a safe drug and can be given safely to the patients.”

Relapsed/refractory (r/r) light chain (AL) amyloidosis remains a particularly difficult disease to treat, and as such great unmet need exists for patients in this population. One potential new treatment option currently in development is Immix Biopharma and its subsidiary Nexcella's NXC-201, an investigational autologous BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy, which is currently being evaluated in the phase 1b/2 NEXICART-2 clinical trial (NCT06097832) in the United States.

, held May 30 to June 3, in Chicago, Illinois. During the conference, 

, interviewed Shahzad Raza, MD, a hematologist/oncologist at the Cleveland Clinic who coauthored the study presented at ASCO, to learn more.

In the interview, Raza explained the background context behind the study and went over the key efficacy and safety results presented at the meeting. He explained that the data presented at ASCO included 7 patients treated with NXC-201 and that the results showed high response rates, with some achieving minimal residual disease negativity by day 25. Although, he pointed out that renal and cardiac organ responses are still being evaluated and more mature data will be needed to evaluate these. With regard to safety, Raza noted that cytokine release syndrome (CRS) and neutropenia have been observed, although these are expected with CAR-T therapies. Although, emphasized that no neurotoxicity has been reported, and characterized the early safety data as exciting.

The hematologist/oncologist at the Cleveland Clinic discussed early results from a clinical trial evaluating the BCMA-directed CAR-T therapy.

This is the second part of an interview with Laura Aguilar MD, PhD. For the first part, 

The chief medical officer of Diakonos Oncology discussed the broader implications of a positive data readout from a trial for the company’s autologous dendritic cell immunotherapy.

Laura Aguilar MD, PhD, on the Potential to Apply Immunotherapy DOC1021 to a Broad Array of Tumor Types

“This could be used for any tumor where we can get a tumor sample and a patient can undergo a leukapheresis procedure to give us their peripheral blood cells. There's a huge opportunity here for a platform technology that could really benefit a lot of patients with a lot of different tumor types. Needing to do a separate trial for each tumor indication is expensive. More funding to be able to test this in more tumor indications will really allow it to, I think, reach its full potential.”

2025 American Society of Clinical Oncology (ASCO) Annual Meeting

, held May 30 to June 3, in Chicago, Illinois, Diakonos Oncology is presenting data from a phase 1 clinical trial evaluating dubodencel (also known as DOC1021), an investigational autologous dendritic cell immunotherapy made from patients’ own tumor cells and peripheral blood mononuclear cells, for the treatment of gliobastoma. Notably, the results showed that the immunotherapy was well tolerated across all 4 dose levels tested and an 88% 12-month survival rate was observed for a group of newly diagnosed patients (n = 16), which was notably higher than what would be expected for the patient population with standard of care treatment.

 held a discussion with Laura Aguilar MD, PhD, the chief medical officer of Diakonos Oncology, 

 In the context of this conversation, Aguilar also went over the broader implications of the new data, and discussed potential future plans to apply the DOC1021 platform to a broader range of tumor types. Aguilar pointed out that a separate phase 1 clinical trial for the immunotherapy is already ongoing at Baylor College of Medicine in pancreatic cancer and pancreatic adenocarcinoma and that Diakonos is getting ready for an additional trial in refractory melanoma. She also touched on how work is currently being done aimed at making the manufacturing process for DOC1021 more efficient.

Laura Aguilar, MD, PhD, on the Potential to Apply Immunotherapy DOC1021 to a Broad Array of Tumor Types

The program director of the center for psychiatric oncology & behavioral sciences at Mass General Cancer Center discussed her presentation at ASCO this year.

Jamie Jacobs, PhD, on Using a Digital App to Aid Caregivers for Patients Undergoing Hematopoietic Stem Cell Transplant

“I think what's really notable about these findings is not just what significant and clinically meaningful improvements we saw in quality of life and some of our other secondary outcomes, but also how engaged caregivers were using this app content.”

For patients receiving many cell-based and other advanced therapies, including hematopoietic stem cell transplant (HSCT), the role of the caregiver is of great importance. This role can have a particularly high burden in the context of patients receiving HSCT for cancer indications. As such, means of effectively reducing caregiver burden, and addressing the psychological impacts of caregiving, are an important area of interest.

, held May 30 to June 3, in Chicago, Illinois, Jamie Jacobs, PhD, the program director of the center for psychiatric oncology & behavioral sciences at Mass General Cancer Center, is giving a presentation entitled “Psychosocial digital application for caregivers of patients undergoing hematopoietic stem cell transplantation (HSCT): A randomized controlled trial.” The presentation covers a clinical trial evaluating the utility of a digital tablet app, referred to as the BMT-CARE App, that provides self-guided modules intended to aid caregivers before, during, and after the patient’s treatment with HSCT.

, Jacobs discussed the results of the trial and their implications. She pointed out that the study, which took place at the Mass General Cancer Center, enrolled 125 caregivers and compared those who received standard care (a single meeting with a social worker) to those who also used the BMT-CARE App. At 60 days posttransplant, caregivers in the group that used the app showed significant improvements in quality of life, reduced caregiving burden, lower symptoms of depression and posttraumatic stress, and better ability to cope with the stress of caregiving. Jacobs concluded that translating a previously clinician-delivered intervention into a scalable mobile format, the BMT-CARE App offers a resource-efficient solution to support caregiver mental health throughout the transplant journey.

REFERENCE
1. Jacobs JM. Psychosocial digital application for caregivers of patients undergoing hematopoietic stem cell transplantation (HSCT): A randomized controlled trial. Presented at the 2025 ASCO Annual Meeting, held May 30 to June 3, in Chicago, Illinois.

The chief medical officer of Diakonos Oncology discussed phase 1 data on the company’s autologous dendritic cell immunotherapy.

Laura Aguilar MD, PhD, the chief medical officer of Diakonos Oncology

“At this point, we have pretty good follow-up on these patients, and what we have seen is a better survival than you would expect.”

Patients with glioblastoma face very limited treatment options and the unmet need for novel treatments is substantial. Diakonos Oncology is currently evaluating dubodencel (also known as DOC1021), an investigational autologous dendritic cell immunotherapy made from patients’ own tumor cells and peripheral blood mononuclear cells, for the treatment of gliobastoma in a phase 1 clinical trial. Notably, the company is presenting data from this study at the 

 interviewed Laura Aguilar MD, PhD, the chief medical officer of Diakonos Oncology, to learn more. Aguilar described how DOC1021 is made and how it is intended to function, and then went over the key results being presented at ASCO this year. She pointed out that the study enrolled 18 patients, including 16 patients who were newly diagnosed and 2 with recurrent disease. DOC1021 was administered via 3 injections into the deep cervical lymph nodes following chemoradiation, but prior to adjuvant temozolomide. Aguilar stated that the immunotherapy was well tolerated across all 4 dose levels, with no dose-limiting toxicities observed.

With regard to efficacy findings, Aguilar explained that investigators observed increased T-cell trafficking to the tumor in posttreatment tumor samples, as well as rises in central memory CD4+ and CD8+ T-cells in the peripheral blood. The 12-month survival ratefor the 16 newly diagnosed patients was 88%, notably higher than would be expected for the patient population with standard of care treatment, given that the group had poor prognostic features, such as being 94% MGMT unmethylated and 25% not having had gross total tumor resections. Aguilar also briefly discussed plans for a recently launched phase 2 clinical trial for DOC1021.

Laura Aguilar, MD, PhD, on Evaluating Immunotherapy DOC1021 for Glioblastoma

The chief executive officer and cofounder of March Biosciences discussed the company’s trial design presentation at ASCO’s 2025 meeting.

Sarah Hein, PhD, on the Phase 2 Trial for CD5-Directed CAR-T MB-105 in R/R T-Cell Lymphoma

“If you're familiar with this indication, unfortunately once patients enter the r/r setting, there really is not a standard of care. These patients have about a less-than-20% survival over about 3 years, and that's because there's a handful of salvage therapies available to these patients, but not a lot else.”

Patients with relapsed/refractory (r/r) T-cell lymphoma currently have few options. As such, the unmet need for new therapies for this indication is quite substantial. One potential candidate to fulfill this role is MB-105, an investigational CD5-directed chimeric antigen receptor T-cell (CAR-T) therapy currently being evaluated for the treatment of r/r CD5-positive T-cell lymphoma. The therapy, which was invented at Baylor College of Medicine and is being developed by March Biosciences, is being evaluated in an ongoing phase 1 clinical trial (NCT03081910) that was launched in 2017 and a phase 2 clinical trial (NCT06534060) that recently launched on February 15, 2025.

, held May 30 to June 3, in Chicago, Illinois, March Biosciences is giving a presentation on the design of the new phase 2 clinical trial. Ahead of the meeting, 

 sat down with Sarah Hein, PhD, the chief executive officer and cofounder of March Biosciences, to learn more.

Hein pointed out that MB-105 targets CD5, a protein expressed in 70% to 80% of peripheral and cutaneous T-cell lymphoma cases, making it broadly applicable. She also noted that the trial, which began enrolling patients earlier this year, uses a Simon 2-stage design and is being conducted at 12 sites across the United States. March Biosciences announced its first patient dosed about a month ago.

Hein highlighted the urgent need for innovative therapies in this space and encouraged physicians to refer eligible patients. She stressed the importance of reaching patients quickly. She also spoke about how while manufacturing and scale-up remain challenges, the company has built infrastructure to support current and future development. Hein additionally emphasized openness to new clinical sites and partnerships.

The last thing that I might add is something that’s decidedly nonimmunologic and that’s that I think we really have to make sure, as a field, and I think this has to be a collaboration between developers and physicians and even payers, both government and private payers, is to make sure that we have access to these therapies.

One of the things that I’ve seen and have been increasingly thinking about is systems and how we succeed is a troubling trend that, first, not everybody has equal access in this country. That’s dictated by racial and socioeconomic and structural features as well as in part by the cost of these therapies and the difficulty of getting them to people. And as we look at individuals, for example, who have received all T-cell therapies including giving CAR T therapies, you start to see more skewing; in other words, traditional factors that affect access, whether it’d be racial or socioeconomic, tend to be exaggerated as we have these high-cost complex technologies that require not being treated in the rural center where you live but getting to an expert like you or me at the H. Lee Moffitt Cancer Center, Tampa, Florida or UCSF [University of California, San Francisco] where you have to take some effort to get there. And it’s going to be harder. Individuals who historically had access barriers whether culturally, educationally, or economically are less likely to get to us.

I would say you’re absolutely right. I don’t think I can add to your thoughtful summary of the immunologic issues, but I want to make sure as we move forward that we do everything we can to make sure that these therapies, which are breakthrough therapies, are keeping people alive longer, already in clinical trials, and will do so even more once they’re approved, get to everybody, and that we work as hard as we can in a collaborative way to make that happen.

I think that’s a great way to end this session. I’d like to thank 

®for having afforded us the opportunity to get TIL [tumor-infiltrating lymphocyte] cell therapy to the forefront. And I’d like to thank my colleague, Krishna Komanduri MD, for sharing his excellent expertise.

Thank you. My brilliant pleasure, and I want to join you in thanking the 

® group and our audience for paying attention this long. Thanks so much.

Closing out their discussion on TIL therapy, Drs Sarnaik and Komanduri identify existing barriers to TIL use in clinical practice and how the field might optimize patient access to these regimens.

Overcoming Barriers to TIL Use in Patients With Solid Tumors

Well, that’s a great segue into our final topic, and that involves future directions. Are there any interesting ongoing either trials or data or concepts that you look forward to seeing with regards to the TIL [tumor-infiltrating lymphocyte] space?

I would say the first thing is that we shouldn’t underestimate the importance of this moment. I mean, it’s been a long time coming. We’ve been talking about cell therapies and gene therapies for a long time, axi-cel [axicabtagene ciloleucel], tisagenlecleucel, and ide-cel [idecabtagene vicleucel] have been absolutely transformative in the setting of CD19 diseases. And lately, we have really remarkable successes in the context of BCMA [B-cell maturation antigen] approaches and now we have TIL therapies. I do think one of the things that we’re going to have to look for is how therapies that require bespoke manufacturing like CAR [chimeric antigen receptor] T-cells and TIL therapy are going to compete with therapies that can quite easily be manufactured at scale like bispecific antibodies that may not have quite the success that TIL therapies or CAR T-cell therapies have, but are a lot easier to manufacture and might not have or won't have, I think, the downside associated with treatment delays.

I think that we’re in a setting and we’re starting to see this in areas like myeloma where we’ve just had a number of dramatic advances. We went from immunomodulatory therapies to proteasome inhibition therapies. Now, we have bispecifics and CARs all competing with other pharmacologic agents. In melanoma, of course, we still have targeted agents that can interfere with MAP [mitogen-activated protein] kinase and MEK [mitogen-activated protein] signaling, for example. I think one of the curious things that we’re going to have to see is how do we as a field come together, sequence therapies, use combination therapies generally as immunologists.

I think that we’re going to be moving further toward combination therapies. And yet those trials are hard to do. These agents are expensive individually, and they’re even more expensive together. So how do we do that and appropriately ask questions as a field in ways that we’re not stepping on each other’s toes and competing with each other as we do these trials? I think that’s going to be a real challenge. I know that that’s not a direct answer to where are we going but I think in a way we have amazing successes and new approved therapies coming and that’s going to create challenges for us as academicians to figure out how to do that. I’m curious if you have any thoughts on that topic or if you can see other obvious directions that we’re going to go in.

I think one of the interesting points you raised is that there’s going to be a lot of competition between agents and how to sequence. I think also how to attribute biological response to the actual agent in question and what I mean by that is it’s good news that our patients are now living much longer with advanced melanoma than 10 years ago. But what you notice is that some of the efficacy may be additive. Somebody gets a PD-1 antibody, and they progress, there still may be a lingering biological effect of that PD-1 antibody because it’s not the PD-1 antibody that’s exerting the response, it’s the effect of the PD-1 antibody on the immune cell. So unlike chemotherapy, where it’s a nonspecific poison and it only works for as long as the drugs in the patient system, immunotherapy is not like that at all.

And I think one of the things that we do need to develop are surrogates for response, readout assays that are beyond just scanning the patient or functional path, or immunologic assays to detect and track a specific antitumor immunologic response from your treatment. And I think if we’re able to do that, we should be able to logically sequence our patient treatment. And we may be able to do that in a patient-specific way. I think we’re still a bit primitive in our clinical trial design where we take a group of 100 patients and treat them not really understanding that well maybe some portion of that patient population would respond to one treatment better than another. If we’re able to build better readout assays to predict which treatment modality would give the best biological effect, that’ll come a long way for us.

The last thing I wanted to mention, tying it back into some of these preclinical abstracts that we’ve discussed, I do think that improving the efficacy of cell therapy on a per cell basis may have a couple of advantages. Number 1, we may not need to treat patients with such large number of TILs that we’re doing now. I think that is one distinction between CAR T and TIL is that CAR T uses a much smaller number of cells and TIL does and in part it could be the target of your CAR T is a lot more amenable than it is for melanoma or non-small cell lung cancer because you need the TIL to traffic outside of the blood supply which you don’t need for CAR T-cell therapy.

And secondly, the need for such intensive lymphodepletion. If we have more potent T cells, we may be able to attenuate or even do away with the lymphodepletion and that would result in our being able to treat more patients and possibly also give repeated cycles of therapy. Right now, we’re limited in our cycles of therapy because the lymphodepletion can cause some permanent bone marrow fibrosis and bone marrow failure. But if we get tumor-specific TIL, we won’t get the on-target off-tumor effect and then we’ll also get the ability for improved efficacy. What are your thoughts about that?

Well, first I’d say, no I consider myself card-carrying immunologist. I don’t think I could do much better than you just did, so I won’t try and riff on what you just said. I think all those things are really critical.

Experts Amod Sarnaik, MD, and Krishna Komanduri, MD, consider lessons learned about TILs and CAR T-cell therapy in hematologic cancers, and how they anticipate TILs fitting into treatment paradigms for solid tumors.

TIL Therapy: Lessons Learned and Potential Future Directions in Care

I think the field also had a bit of a setback in the last few weeks. Another abstract that was reported on was about the design of the DELTA-1 trial, which was another TIL [tumor-infiltrating lymphocyte] trial, in patients who had failed primary therapy with checkpoint inhibitors, and MEK inhibition if BRAF associated. Unfortunately, we got the news just a couple of weeks ago that Instil Bio, the sponsor of that trial, is suspending its lead product, ITIL-168, and has had a significant commercial setback. We don’t know to what extent that will affect the development of other products that are competing. I certainly think it’s always good from my perspective, from an academic perspective, to have healthy competition driving success and providing more options for patients. I think we’re all not yet cognizant of what the factors were, but that’s a bit sad.

We do think the trial you did, and the work that’s happening should lead to an approval sometime. Again, being optimistic and having no idea of what the FDA is exactly thinking, but we’re hopeful that there will be an approved TIL therapy in 2023 for patients who have failed prior melanoma therapies.

Excellent. I think time permits a couple more abstracts to be discussed, and you as an immunologist should be uniquely poised to answer them. There was an abstract at SITC [Society for Immunotherapy of Cancer annual meeting] by Carmela Passaro, PhD, et al, involving TILs expressing IL-15 [interleukin-15] along with other cytokines. Please comment.

So a couple of things. I think one of the other abstracts we were going to talk about is the interaction between natural TIL expansion and things like checkpoint inhibitors that regulate how T cells respond. We know that checkpoint inhibitors obviously have a role broadly in human cancers across the solid tumor spectrum. Some pioneering work by Arlene Sharpe, MD, PhD, looked at the role of PD-1 signaling in the TILs, which was also reported at the SITC meeting, and the idea that perhaps if we modulated PD-1 signaling in TILs as they’re being expanded, that could lead to optimized expansion approaches. So this abstract by and colleagues; we talked about the role of IL-2 administered in patients to lead to the survival and expansion of the TILs following an infusion of the patient. But it’s also important to note that IL-2 is used to expand almost all categories of T cells that are in commercial therapies. IL-2 is used in CAR [chimeric antigen receptor] T cell manufacture, it’s used in antivirus-specific T-cell manufacturing. And it is one of the things that is used to expand T cells outside the body in the TIL manufacturing process.

What this group did was use some genetic transduction methods to express other molecules that are also important in T-cell expansion, and that included IL-15 and IL-18, and they had an undisclosed member of the TNF [tumor necrosis factor] receptors family that was also used. All these approaches in conjunction with interferon alpha were used to basically optimize the expansion of the TIL product.

Now, I would say none of this from my perspective is quite ready for prime time, but it tells us, and you thoughtfully mentioned earlier, that the TIL is not common from person to person. The T cells that are around my tumor might be different from the T cells around your tumor. They might have different ratios of CD4 to CD8 cells, regulatory T cells, or other cells. By optimizing the manufacturing environment, it’s very likely that we’ll over time improve the speed of manufacturing, the reliability of manufacturing, and I think the subsets of T cells. You mentioned, for example, in the preclinical analysis that you had done, that if you had more TILs at the end of the product manufacturing time, that was likely something that should theoretically affect clinical responses in vivo.

I think this is an interesting look forward into ways we could use better engineering approaches to generate a better TIL product. I think associated with that, there were a couple of other interesting abstracts where, again, we’ve talked about the interplay between checkpoint inhibitors, not only in patients that relate to their prior responses, but the notion that checkpoint inhibitors on the TILs themselves might be modulated in vitro to get better expansion. Another abstract by Colin Thalhofer, PhD, looked at silencing using an RNA [ribonucleic acid] interference approach of PD-1, which again led to better expansion and potentially the function of those T cells in a more rich and functional product that can be infused.

I think these are some exciting approaches. For all of us who are both clinically and scientifically oriented in this field, as you and I both are, we want to see an approved product go to patients, and we want to see that effectively manufactured and reach patients, and provide a treatment alternative. But I think it’s clear once we have that, there are a number of things that are iterative that can be done in the pipeline to manufacture better products. To more reliably manufacture products, it could be that some patients won’t have a product that’s manufactured, and some of these theoretical approaches might lead to more reliable or successful product manufacturing in a shorter period of time. All of the factors that you talked about are going to be critical for us as we move forward.

Shared insight from Amod Sarnaik, MD, and Krishna Komanduri, MD, on the halted DELTA-1 clinical trial of ITIL-168 in melanoma, followed by a focused discussion of SITC 2022 data on emerging TIL design and manufacturing strategies.

Data from Additional Clinical Studies on Tumor-Infiltrating Lymphocyte Therapy

The next abstract we would like to discuss is a multicenter, single-arm, phase 2 study involving TILs [tumor-infiltrating lymphocytes] in the treatment of advanced treatment-refractory melanoma. This was a study that was sponsored by Iovance [Biotherapeutics]. The study had 153 patients, so it’s the largest study of TILs in melanoma that we’re aware of. The patients were heavily pretreated with 3 median lines of prior therapy. The reported response rate was 31%.

Expert perspectives on results from C-144-01, which utilized the TIL therapy lifileucel in the setting of metastatic melanoma, and situations in which the regimen might be used in clinical practice.

Oncology

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