Review highlights engineering advances and toxicity mitigation for T-cell bispecific antibodies in cancer therapy, indicating key pathways to improve next-generation immunotherapies.
Key Points
To review molecular engineering advancements, clinical toxicity management, and translational strategies for CD3-engaging bispecific antibodies in hematologic and solid cancers.
Synthesized molecular engineering strategies including format optimization, affinity modulation, selectivity enhancement, and half-life extension via Fc- or albumin-based designs.
Evaluated clinical management protocols for cytokine release syndrome, including step-up dosing, corticosteroid premedication, and tocilizumab intervention.
Assessed emerging architectures including trispecific antibodies, BiTE-CAR hybrids, and logic-gated conditional binding systems.
Fc- and albumin-based modifications address the rapid clearance of traditional Fc-less bispecific antibodies by leveraging FcRn-mediated recycling to prolong serum half-life.
Systemic immune toxicities, predominantly cytokine release syndrome, are effectively mitigated using step-up dosing regimens, preventive corticosteroids, and targeted IL-6 receptor inhibition with tocilizumab.
Conditional activation models and logic-gated architectures enhance selectivity against tumor-associated antigens, showing promise for improving safety and efficacy in solid tumors.