CAR-T细胞,脑瘤 z-bo 2020-09-30 370

　　In a new study, researchers from Massachusetts General Hospital and Harvard Medical School have discovered an exciting new type of cancer immunotherapy for patients with glioblastoma, which is the most common and deadly brain. They established a new method that can make immunotherapy effective against brain tumors again, which may help it be used to treat other types of solid tumors. This immunotherapy, called "Chimeric Antigen Receptor T Cell Therapy" (CAR-T), collects immune-aggressive T cells from patients and genetically modifies them to identify specific tumors on the surface. Reinject the target (antigen) into the same patient. Two CAR-T cell products have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of non-Hodgkin’s lymphoma and acute lymphoblastic leukemia, representing lymphoma and blood cancer, respectively.

　　The corresponding author of the paper, the head of cellular immunotherapy at Massachusetts General Hospital, and the medical assistant professor of Harvard Medical School, Dr. Marcella V. Mouse, said that the traditional anticancer drug is glioblastoma. He explained that it is difficult to treat such as solid tumors. Most drug molecules are too large to cross the blood-brain barrier, so immunotherapy also has problems in this regard.

　　Maus said: “In the past, we created CAR-T cells for the treatment of glioblastoma. One of the challenges facing glioblastoma is that all tumor cells are targeted by T cells.”

　　The target is epidermal growth factor receptor mutant III (mutated oncoprotein that exists on the surface of many but not all glioblastomas". EGFRvIII). Therefore, in order to improve the efficacy of CAR-T cells, they decided to target the first Two types of antigens are naturally occurring EGFR or "wild" EGFR. However, considering that EGFR is present in many cells of the human body, drugs targeting this protein can cause serious side effects. To overcome this toxicity problem, Maus et al. CAR-T cells that can be transported to the cerebrospinal fluid at the bottom of the brain. Once in the brain, these CAR-T cells secrete another type of immunotherapeutic molecule called bispecific T-cellengager (BiTE). BiTE is one An antibody that induces cell-killing T cells to a specific target is somewhat similar to the so-called "smart bomb" automatic inducer. BiTE is smaller than antibody drugs, but even if injected intravenously, BiTE is still too large to cross the blood-brain barrier Therefore, constructing a CAR-T construct for the secretion of BiTE is the second goal. This antigen produces local tumor effects. This is a way to overcome tumor heterogeneity and target both substances. However, it is Other organs are toxic because it is produced in small amounts on the other side of the blood-brain barrier." When tested in a human glioblastoma model, it was found that these modified CAR-T cells that secrete BiTE can eliminate about 80% of tumors. .

　　The lead author of the paper, Dr. Brian D. Choi, a neurosurgery researcher at Massachusetts General Hospital, said that the technology is expected to treat other solid tumors. These researchers said that the biggest obstacle they face when conducting this research into human clinical trials is still financial support.