CYNK-101 Demonstrates Anti-Tumor Activity in HNSCC Cells

Article

The NK cell therapy is also being evaluated in a phase 1 study for acute myeloid leukemia.

The allogeneic natural killer (NK) cell therapy CYNK-101 has shown promising anti-tumor activity for EGFR+ lung cancer and head and neck squamous cell carcinoma (HNSCC) in preclinical studies.1,2

Data from Celularity’s CYNK-101 program were presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021 by first author Irene Raitman Khutorskoy, PhD, principal scientist, Celularity.

“The human epidermal growth factor receptor (EGFR) has been found to be overexpressed in 40-90% of non-small cell lung cancers, with squamous cell carcinomas making up the larger proportion, and in as many as 80% of invasive HNSCC; often translating to a worse outcome for patients,” Khutorskoy and colleagues wrote.2

Khutorskoy and colleagues assessed the antibody dependent cellular cytotoxicity of CYNK-101 in combination with cetuximab against EGFR+ NSCLC and HNSCC cell lines. They first transduced human placental CD34+ cells with a lentivirus expressing CD16VP. The cells were then expanded with cytokines to generate the CYNK-101 cells. They also used Wortmannin, a PI3K kinase inhibitor, to investigate CYNK-101's mechanism of cytotoxicity.

READ MORE: New Collaboration to Develop ROR1 Targeted Cell Therapies

The investigators observed anti-tumor activity by CYNK-101 with cetuximab in vitro. They found that CYNK-101 had greater cytotoxicity with cetuximab than with control in cultured cell lines (P <.05). Analysis with Wortmannin also revealed that CYNK-101's cytotoxicity is PI3K pathway-dependent.

“CYNK-101 cells provide a combination immunotherapy option by harnessing the anti-tumor activities of both targeted biologics and innate cytotoxicity of NK cells. Further development of CYNK-101 in combination with the therapeutic antibody for these solid tumor indications is warranted,” Khutorskoy and colleagues concluded.2

Another of Celularity's candidates, CYNK-001, is being assessed in a phase 1 clinical trial (NCT04310592) that expanded its enrollment from patients with minimal residual disease (MRD) to also include patients with relapsed/refractory acute myeloid leukemia (AML).3

The expansion was prompted by a patient conversion from MRD-positive disease to MRD negativity. The patient had NPM-1–positive, FLT3-negative AML and had received the highest dose level of 5.4 billion CYNK-001 cells. The patient did not experience a dose-limiting toxicity (DLT) and had good-risk cytogenetics.

“The demonstrated ability to deliver a total [natural killer] cell dose of 5.4 billion cells in the outpatient setting without DLT and the observation of achieving a conversion from an MRD-positive to MRD-negative state on bone marrow examination with CYNK-001 cells persisting in bone marrow and blood at 28 days after day 0 infusion, is compelling and supports our trial dose escalation and indication expansion,” Robert J. Hariri, MD, PhD, founder, chairman, and chief executive officer, Celularity, said in a statement at that time.3

For more coverage of SITC 2021, click here.

REFERENCES
1. Celularity presents preclinical data on allogeneic genetically-modified natural killer cells at the Society for Immunotherapy of Cancer 36th Annual Meeting. News release. Celularity. November 15, 2021. https://celularity.com/celularity-presents-preclinical-data-on-allogeneic-genetically-modified-natural-killer-cells-at-the-society-for-immunotherapy-of-cancer-36th-annual-meeting/
2. Raitman I, Fitzgerald J, Rousseva V, et al. Developing placental CD34+-derived natural killer cells with high affinity cleavage resistant CD16 (CYNK-101) and Cetuximab for enhanced therapy of EGFR+ non-small cell lung and head and neck cancers. Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington, DC. Abstract 159
3. Celularity announces expansion of human placental hematopoietic stem cell derived natural killer cells (CYNK-001) phase 1 trial in patients with acute myeloid leukemia. News release. Celularity. June 29, 2021. Accessed November 15, 2021.
Related Videos
Xandra Breakefield, PhD, on Trying New Approaches to AAV Therapy for Glioblastoma
Nathan Yozwiak, PhD, on Researching AAV Gene Therapy Delivery to the Brain
Zheng-Yi Chen, DPhil, on International Collaboration on Clinical Trials
Janice Chen, PhD, the cofounder and chief technology officer of Mammoth Biosciences
Maria Escolar, MD, the chief medical officer of Forge Biologics
Leigh Ramos-Platt, MD, on Allowing Access and Ensuring Preparation for Gene Therapies
John Murphy, PhD, the chief scientific officer of Arbor Biotechnologies
Erika Fullwood Augustine, MD, MS, the associate chief science officer of the Kennedy Krieger Institute
Maria Escolar, MD, the chief medical officer of Forge Biologics
Casey Maguire, PhD, associate professor of neurology and associate investigator of neurology, Harvard Medical School
© 2024 MJH Life Sciences

All rights reserved.