IMiDs Augment CD3-Bispecific Antibody–Induced CD8þ 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 CD8þ 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 CD4þ T cells. Our studies provide mechanistic insight into the costimulatory properties of IMiDs and support combination treatments with T-cell agonist therapies in a broad spectrum of indications.