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While the results of CAR-T cell therapy for B-cell malignancies are very encouraging, the treatment of solid tumors in children in a similar way has limited efficacy.
the success rate of CAR-T cell therapy for solid tumors is multi-factor.
identification of tumor-related antigens (TAA) and minimal non-tumor side effects is one of the main challenges.
so far, CAR-T cell clinical trials have shown severe toxicity or minimal efficacy in adult solid tumors.
the current ability to use preclinical models to predict clinical toxicity of chisellular antigen-infested (CAR) T cells in solid tumors is weak, so we need to develop and evaluate gate-controlled systems.
recently, researchers found that mice with GD2 CAR-T cells, specific to tumor-related antigen GD2, induced fatal neurotoxicity by co-regulating domain dependence.
, human B7H3 CAR-T cells showed efficacy in preclinical models of neuroblastoma.
in search of a better CAR, the researchers built a SynNotch gate-controlled CAR-T, GD2-B7H3, which identifies GD2 as the gate and B7H3 as the target.
GD2-B7H3 CAR-T cells control the growth of neuroblastoma in in-body and metastase heterogeneic transplanted mouse models, with high specificity and effectiveness.
these improvements are partly those resulting from better metabolic adaptability of GD2-B7H3 CAR-T cells, as evidenced by their naïve T-like cytotoxic oxidation metabolism and lower depletion.
