Platelets subvert antitumor efficacy of T cell-recruiting bispecific antibodies.

ABSTRACT: T cell-based immunotherapy, for example, with T cell-recruiting bispecific antibody (bsAb), has revolutionized oncological treatment. However, many patients do not respond to treatment, and long-term remissions are still rare. Several tumor immune evasion mechanisms have been reported to counteract efficiency of T cell-engaging therapeutics. Platelets largely affect cancer pathophysiology by mediating tumor invasion, metastasis, and immune evasion. On treatment of patients in a clinical trial with a PSMA×CD3 bsAb (NCT04104607), we observed profound treatment-associated platelet activation, mirrored by a decrease of total platelet count. On modeling the treatment setting, we found that platelet activation significantly reduced bsAb-mediated CD4⁺ and CD8⁺ T-cell reactiv

SUBMITTER: Lutz MS 

PROVIDER: S-EPMC8811601 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature