New CAR-T cells can produce bispecific antibodies that "bite to death" fatal brain malignancies

Glioblastoma is the most common malignant tumor of the brainThis kind of cancer is extremely aggressive, will rapidly worsen, after diagnosis left patients only about 15 months, 5 years survival rate of less than 10%, on the ferocity, than the so-called "king of cancer" pancreatic cancer! Conventional surgery, radiotherapy and chemotherapy have limited effect on the treatment of glioblastomarevolutionary technologies such as immunotherapy and cell therapy have given scientists a more powerful weapon against cancerFor example, the Chimeric Antigen Receptor (CAR) T-cell, a genetically engineered immune cell with a specially designed antibody on the surface that identifies cancer cellsTwo CAR-T cell therapies, such as Novartis's Kymriah and Gilead's Yescarta, are used to treat blood tumors in combination with cancer cell surface antigen CD19picture source: 123RFthe cell surface of glioblastoma, there are also special receptor molecules that can be used to identify antigensFor example, the epidermal growth factor receptor EGFRvIII in the form of mutationThese "carcinogenic receptors" mediate abnormal growth factor signaling pathways that drive cancer cells to grow uncontrollablelytheoretically, CAR-T cells could be allowed to identify EGFRvIII and attack glioblastomaThat's exactly what Professor Marcela Maus, who led the study, triedBut the reason for the difficulty of solid tumors is that "heterogeneity", that is to say, the molecular characteristics of these cancer cells are not the sameIn glioblastoma, there are many cells that do not express the mutated form of EGFR, but a large number of expressions of normal EGFR, they also amplify the growth signal, causing the tumor to grow madAt this time, car-T cells identified by EGFRvIII alone cannot repel tumorsHow canmake up another punch and improve the effectiveness of treatment? At this time, the new immunotherapy - bi-specific T-cell joint (BiTE) on the sceneThe so-called "bispecific", is that can target two molecules at the same time, it is like two molecules hook, one bites the tumor cell EGFR, the other bites the effect of The Surface antigen on the T cell, the T cell activated, so that it produces a protein that can kill the tumor But biTE has a role to play, and there is a problem to be solved: glioblastoma is located in the brain, and antibodies have to pass through the blood-brain barrier to work, which is difficult for biTE with a large molecular weight to this end, the research team designed a creative approach They introduced the gene that expresses BiTE into CAR-T cells, which, when they enter the brain, continue to produce BiTE "bite" tumor cells CAR-T cell schematics that express bispecific antibodies (Photo: Supplied) the team tested the therapeutic potential of this new CAR-T cell in a mouse model of glioblastoma they implanted human glioma cells into the brains of immunodeficiency mice and then injected CAR-T cells that secrete BiTE into mice, while targeting tumor cells that expressed EGFRvIII and EGFR Over a period of 3 weeks, 80% of the mice showed "complete remission" and no tumors were visible in their bodies! the secretion of THE CART-EGFRvIII cells targeted at EGFR, allowing tumors in the brains of mice to shrink or even disappear completely within 3 weeks (Photo: Source: 1) in addition, because BiTE for EGFR plays a role in the area where CAR-T cells arrive, without affecting other normal tissues expressing EGFR, the researchers also tested the safety data for the treatment researchers have patented the CART.BiTE cell and hope to conduct further clinical trials Like other cancer treatments, the new treatment needs more experimental evidence before it is finally confirmed to be suitable for human use "Given the very low survival rate for glioblastoma, any effective treatment, even for a fraction of cases, can benefit patients Professor Maus believes References: Nature Biotechnology DOI: 10.1038/s41587-019-0192-1 Origind Jul 23, 2019, from https:// original title: "Nature" sub-issue: 80% of mouse tumors completely disappear! New CAR-T cell 'bites to death' fatal brain tumor