Computer-guided dosing of multi-specific T-cell immunotherapy

Researchers have been seeking ways to overcome the limitations of conventional T-cell immunotherapies, which are often hindered by patient-specific tumor heterogeneity. The authors report on a modular split-antibody T-cell engager platform called MATCH and a computational framework called COMPASS that predicts individualized multi-specific therapy compositions. COMPASS integrates various factors such as T-cell counts, tumor burden, and antigen expression to identify optimal dose combinations that maximize tumor cell killing while preserving T-cell viability. The framework was tested on chronic lymphocytic leukemia patient PBMC samples and successfully predicted effective formulations for a human lymphoma xenograft murine model, leading to improved survival rates. This approach provides a generalizable blueprint for precision T-cell immunotherapy and offers a new paradigm in patient-specific cancer treatment.