Clinical City of Hope & Mustang Bio’s CAR-T Therapy Shows...

City of Hope & Mustang Bio’s CAR-T Therapy Shows Promising Phase 1 Results

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For patients with recurrent glioblastoma, the chimeric antigen receptor T-cell (CAR-T) treatment developed by Mustang Bio and City of Hope was successful in a phase 1 clinical study; 50% of patients achieved disease stability or better, and one patient has been cancer-free for almost five years.

The biggest published trial on a CAR-T treatment in glioblastoma to date was detailed in Nature Medicine. This study adds weight to the argument for the viability and potential benefits of a new approach to treating brain tumors—injecting CAR-T cells straight into the tumor itself and the cerebrospinal fluid.

Christine Brown, the deputy director of T Cell Therapeutics Research Laboratories at City of Hope, remarked, “I think a lot of our findings are reshaping the field and how we’re thinking about applying cell therapy to brain tumors. This paper both sets the foundation clinically, but also tries to get at some of the features of glioblastoma that make it difficult to treat, including with immunotherapy.”

The most prevalent and deadly primary brain tumor is glioblastoma, which is also called glioblastoma multiforme. Without treatment, the median survival time for the first incidence is approximately nine months. Unfortunately, malignancies return exceedingly resistant than before, so that number only climbs marginally with treatment to around 12 to 14 months.

Before participating in the experiment, all 58 participants in the first phase had encountered a recurrence. The majority of patients were receiving treatment for their third. The standard for cancer treatment—a mix of surgery, chemotherapy, and radiation—had already been administered to them.

Every participant in the study was given a weekly dosage of CAR-T cells that targeted the antigen interleukin-13 receptor alpha 2, or IL13Rα2. This particular target has a long history of use in glioblastoma and has been investigated both in the lab and in clinical settings for CAR-T treatment, including in an earlier phase 1 trial conducted by the research group at City of Hope led by Brown and Badie. The therapy is now being developed by Mustang Bio, which has obtained the necessary licenses.

Over the course of the experiment, patients were given progressively greater dosages using a variety of modalities, including injections into the tumor, infusions into the cerebrospinal fluid, or a combination of the two for the last group. Patients who were already enrolled and had CAR-T cells remaining could be allowed to receive infusions of these cells so long as they were eligible.

Researchers were first concerned that something bad might occur if they injected CAR-Ts directly into the brain, because systemic administration of CAR-T therapy has been associated with harmful side effects in the brain.

Surprisingly, no patient had neurotoxicity. According to Badie, the only negative effects experienced by some were temporary fevers and headaches. The reason behind this is that, in contrast to other kinds of CAR-Ts aimed at the CD19 antigen, the IL13Rα2 receptor is generated mostly by tumors and small groups of inflammatory cells, rather than neurons or cranial nerves.

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