IMiDs Augment CD3-Bispecific Antibody-Induced CD8+ T-Cell Cytotoxicity and Expansion by Enhancing IL2 Production.

ABSTRACT: Although CD3-bispecific antibodies have shown promising activity in the treatment of hematological cancers, insufficient T-cell costimulation may limit long-term responses. Immunomodulatory drugs (IMiDs), routinely used in treating multiple myeloma, possess pleiotropic antimyeloma properties and have been described to enhance T-cell responses similar to costimulatory signaling and may therefore have synergistic effects when combined with T-cell bispecifics. In this report, we demonstrate that IMiDs substantially enhance tumor cell killing induced by CD3 bispecifics and increase CD8+ T-cell proliferation and expansion. We further show that the beneficial effects of IMiDs on T-cell function and expansion are mediated by enhanced IL2 production by CD4+ T cells. Our studies provide mechanistic

SUBMITTER: Li J 

PROVIDER: S-EPMC10157361 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature