IMiDs augment CD3-bispecific antibody induced CD8+ cell cytotoxicity and expansion by enhancing IL-2 production

Abstract Although CD3-bispecific antibodies have demonstrated promising activity in the treatment of hematological cancers, insufficient T cell co-stimulation may limit long-term responses. Immunomodulatory drugs (IMiDs), routinely used in treating multiple myeloma (MM), possess pleiotropic anti-myeloma properties and have been described to enhance T cell responses similar to co-stimulatory 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 IL-2 production by CD4+ T cells. Our studies provide mechanistic insight into the co-stimulatory properties of IMiDs and support combination treatments with T cell agonist therapies in a broad spectrum of indications.