Mustang Bio, Mayo Clinic Collaborate on New CAR T Platform


Mustang Bio plans to file an IND and start a phase 1 clinical trial as soon as a lead construct is identified.

Mustang Bio is collaborating with Mayo Clinic to develop novel chimeric antigen receptor (CAR T) cell technology.1

A new CAR T-cell platform developed by principal investigator Larry R. Pease, PhD, and his lab at Mayo Clinic uses a 2-step approach, with a peptide first administered to the patient to increase their T cell proliferation. Then, the CAR viral construct is administered directly into the lymph nodes of the patient, where they will infect the activated T cells and form CAR T cells in vivo.

Successful use of the platform may mean the development of an off-the-shelf product with no need to isolate patient cells and expand ex vivo.

"We are excited by the possibilities that this novel technology has to offer given our ongoing development of CAR T cell therapies in hematologic and solid tumor cancers," said Manuel Litchman, MD, president and chief executive officer, Mustang Bio, in a statement.1 "The potential use of this technology to facilitate how these treatments are delivered to patients can lead to earlier treatment post diagnosis, and using an off-the-shelf therapy may reduce the cost of care, all of which would help bring more innovative treatments to a broader base of patients in need."

WATCH NOW: Investigating CAR T in Lymphoma, Leukemia, and Solid Tumors

Mayo Clinic has established proof-of-concept in preclinical studies and will continue to develop the platform. Once they have identified a lead construct, Mustang Bio will file an investigational new drug application and plan for a phase 1 clinical trial across multiple centers.

"The immune cells are activated in vivo using the natural methods employed by the body to deal with infection rather than the artificial activation used to manufacture traditional CAR T cells ex vivo," Pease added.1 "This could potentially reduce the substantial toxicities that are characteristic of traditional CAR T therapy."

GeneTherapyLive previously spoke to Litchman about the company’s CAR T-cell therapy pipeline. He discussed a licensing agreement the company has with Nationwide Children’s Hospital for another CAR T product, MB-108, that is being developed for the treatment of glioblastoma multiforme. The product is a next-generation oncolytic herpes simplex virus that previously received orphan drug designation from the FDA in 2019.2

The therapy is designed to target tumor cells while sparing healthy cells and also propagating more virus within tumor cells. The first patient was dosed in the phase 1 clinical trial (NCT03657576) of MB-108 in October 2019. The study, which is being conducted at University of Alabama Birmingham, is continuing to recruit participants. It is primarily evaluating adverse events but also survival and other biomarkers of disease severity. Watch part of our conversation with Litchman below.

1. Mustang Bio collaborates with Mayo Clinic on novel CAR T technology. News release. Mustang Bio. August 12, 2021.
2. Mustang Bio announces dosing of first participant in Phase 1 Clinical Trial of MB-108 (Oncolytic Virus C134) to treat glioblastoma. News release. Mustang Bio. October 24, 2019. Accessed August 19, 2021.
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