Costimulatory CD28 bispecific antibodies synergize with conventional and targeted chemotherapy to elicit potent anti-tumor responses II

Here, we demonstrate for the first time that TAAxCD28 bispecifics synergize with both conventional and targeted chemotherapy agents to significantly enhance antitumor efficacy in humanized murine tumor models.

Mechanistically, an EGFRxCD28 bispecific, when combined with 5-fluorouracil (5-FU). Promotes the expansion and clonal diversification of tumor-infiltrating effector CD8+ T cells, which associates with markedly improved tumor growth control and survival benefit. Further, the combination therapy reprograms the immunosuppressive tumor microenvironment, by rewiring suppressive tumor myeloid cells to immunostimulatory phenotypes, upregulating costimulatory molecules, and increasing the expression of intratumoral proinflammatory cytokines and chemokines.