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A2CAR5 is a high-affinity chimeric antigen receptor (CAR) T-cell therapy targeting the CD5 antigen, specifically developed for the treatment of CD5-positive T-cell malignancies such as T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL). Because CD5 is naturally expressed on healthy T cells, A2CAR5 initially faced significant challenges with fratricide (self-killing) and excessive cytokine release during manufacturing. To resolve these issues, the therapy utilizes CRISPR/Cas9 gene editing to knock out the endogenous CD5 gene, which prevents fratricide and reduces T-cell exhaustion. Furthermore, the TRAC (T-cell receptor alpha constant) gene is knocked out to create an allogeneic, "off-the-shelf" platform. Compared to lower-affinity constructs like C7CAR5, A2CAR5 demonstrates superior cytotoxic engagement and functional persistence against CD5-positive malignant cells once the fratricide mechanism is mitigated.
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