Mustang Bio & City of Hope: CAR-T Cell Therapy Extends Treatment Refractory Glioblastoma Survival

1. Half the individuals receiving the new CAR-T cell therapy achieved stable disease or better.
2. Intratumoral, intraventricular, and intratumoral + intraventricular administration routes all were generally well tolerated.

The Latest

A recent phase 1 clinical trial by Brown et al. and funded by Mustang Bio and City of Hope investigated CAR-T cell therapy for the treatment of refractory glioblastoma. They found their CAR-T cell therapy was safe and efficacious in targeting the IL-13Rα2 receptor in malignant glioblastoma cells. What makes this interesting is that stable disease or better was achieved in half of all patients, which were treatment refractory, through locoregional administration of CAR-T cell therapy. A previous smaller phase 1 trial by Brown et al. in 2022 showed the initial safety and efficacy of IL13Rα2-targeting CAR-T cell therapy in treating glioblastoma. Initially, a 2021 preclinical study by Kim et al. showed the first hints of this therapy in targeting malignant glioma cells and sparing cells expressing IL13Rα1 receptors.

Physicians Perspective

Glioblastoma multiforme (GBM) is a type of cancer that develops in the brain from glial cells, more specifically, astrocytes. According to the American Association of Neurological Surgeons (AANS), GBM has an incidence of 0.00321% and is the most common malignant brain tumor. This highly malignant cancer has a two-year survival rate of 17% after diagnosis. Currently accepted treatments for GBM only include surgical resection, radiation therapy, chemotherapy with temozolomide, glucocorticoids, or a combination of the listed therapies. Particularly, adjuvant temozolomide therapy alongside radiation therapy showed the longest median survival of 9.3 months. CAR-T cell therapy provides a unique approach to extending survival for an aggressive malignancy which quickly degrades patient quality of life and offers itself as an option for treatment refractory glioblastoma.

Molecular Target of Therapy

As mentioned, Mustang Bio and City of Hope developed a CAR-T cell therapy that targets the IL-13Rα2 receptor. This receptor is mainly found exclusively in glioblastoma cells and is not commonly found in other human cells. Just like other CAR-T cell treatments, this therapy works by first harvesting autologous T lymphocyte cells. Afterwards, using a viral vector, these autologous cells are infected and made to express a Chimeric Antigen Receptor (CAR). Specifically for this therapy, T lymphocytes were made to express the IL-13Rα2 receptor, which is almost exclusively found in glioblastoma cells, allowing for T cells to mount a direct attack on the tumor.

Company History

This therapy was developed by Mustang Bio in collaboration with City of Hope. Mustang Bio is also in the process of phase 1 clinical trials for CAR-T cell therapies for hematological malignancies such as Non-Hodgkins Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). Mustang Bio has derived a large portion of its funding from a recent $75 million debt financing deal with Runway Growth Capital.

Further reading: https://www.nature.com/articles/s41591-024-02875-1

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