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CD3ε CAR-T refers to chimeric antigen receptor (CAR) T cells engineered with the intracellular domain (ICD) of CD3ε (often in second-generation constructs with 4-1BB costimulation, termed BBε CAR) replacing or augmenting the conventional CD3ζ ICD. This modification leverages the CD3ε ICD's single ITAM and unique signaling motifs (e.g., basic-rich stretch, proline-rich sequence) to enhance anti-tumor performance, showing superior in vivo tumor control, improved persistence, reduced exhaustion, and better metabolic profiles (e.g., glycolysis, OXPHOS) compared to standard BBζ CAR-T cells in preclinical models like Nalm6 xenografts. Developed through systematic engineering of CD3 complex components, it addresses limitations of traditional CAR-T by optimizing activation, degranulation, and resistance to dysfunction while mitigating tonic signaling; no specific developer or clinical trials are identified, positioning it as an investigational advancement in CAR design for broader cancer applications.[5][1][3]
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