A new clinical trial in glioblastoma has been launched based on an innovative immunotherapeutic technique – the CAR T cell which can modify then harness a patient’s own T cells to fight their disease.
Immunotherapy news (including our blog) often focusses on checkpoint inhibitors like anti-PD-1 and anti-CTLA-4 antibodies, as they make important leaps forward in providing new therapies for a range of cancer patients. The immunotherapy field is obviously much larger than this, and other approaches such as therapeutic vaccines are also showing efficacy in different cancer types. Another treatment type which created a lot of news last week, is chimeric antigen receptor T cells (or CAR T cells) which, following promising preclinical results, are moving into Phase I study in glioblastoma.
What is CAR T cell treatment?
CARs are synthetic molecules which are designed to redirect patient T cells to specific antigens e.g. in cancer immunotherapy, T cells are modified to express receptors which are specific to a particular form of cancer, and which are not found on ‘normal’ tissue. When the CAR T cells are given to patients, they recognize and kill the specific cancer cells without harming other parts of the body. In cancers of the blood (such as disease of the B cells), CAR T cells have been shown to cause long-term, durable disease remission, but moving this into solid tumor therapy has been limited by the lack of targets which are found only on cancer cells.
Exciting new preclinical work published last week in Science Translational Medicine has made the move into the solid tumor world of glioblastoma, specifically for patients with the EGFRvIII mutation. This mutation is thought to be tumor-specific, and is the most common EGFR variant found in human tumors. It is seen in around 30% of glioblastoma patients, and is linked to their poor long-term survival. No current treatments for this specific cancer type can cure the disease, with median survival for people newly diagnosed with glioblastoma being less than 15 months, meaning that new therapies are urgently needed.
CAR T therapies for this specific cancer type have been described before. The new research focused on making sure the CAR T cells were highly specific, didn’t react with wild type EGFR, and were humanized to prevent human anti-mouse antibody responses. The resulting CAR T cells were then tested preclinically in xenogeneic subcutaneous and orthotopic mouse models of human EGFRvIII+ glioblastoma, with results measured by MRI and bioluminescent imaging. Single agent CAR T cells were able to eliminate the glioblastoma tumor, and an even deeper tumor regression was seen when used in combination with temozolomide, which is a current therapy to treat the disease.
The results have been positive enough to open a Phase I clinical trial with this agent, enrolling 12 patients with either recurring disease or patients with residual disease following initial surgery. Patients will have some of their T cells removed and engineered using a viral vector to be able to find cancer cells expressing EGFRvIII. These engineered cells are then infused back into the patients, to proliferate and search out the cancer cells of interest, hopefully sparing normal cells.
Crown Bioscience are excited to see more new immunotherapies and techniques moving into clinical trial, especially for cancer types that need new treatment options. Crown Bioscience support research in immune therapies with a range of immunotherapy platforms (with either murine or human immunity) in a variety of different cancer types (including brain cancer), with syngenic models (including bioluminescent and metastatic models), GEMM, MuPrime™ (the murine version of HuPrime® which is the world’s largest collection of well-characterized and validated Patient-Derived Xenograft models), HuMice™ (humanized mice produced through inoculating human hematopoietic cells into immunocompromised mice), and MiXeno™ (creating transient human immunity by mixing human peripheral blood mononucleated cells with xenograft models). We also support glioblastoma research through the use of our clinically relevant Xenograft and Patient-Derived Xenograft models available for drug discovery and translational sciences.
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