Antibodies to EGF Receptor Family Members Can Upregulate Tumor Immunity

Immunologic mechanisms influence how a cancer patient responds to therapy. Monoclonal antibodies (mAbs) to the epidermal growth factor receptor are clinically approved, and a lung cancer vaccine inducing antibodies to epidermal growth factor (EGF) has some beneficial clinical effects. We tested the hypothesis that mAbs to epidermal growth factor receptor, EGF, and tumor growth factor alpha (TGF-α), in addition to any other effects, can facilitate the generation of a tumor-destructive immunologic response. Data from studies with mouse tumors showed that all 3 of these mAbs stimulated the in vitro generation of a Th1 response with tumor cells killed by spleen cells from mice with SW1 melanoma, B16 melanoma, or ID8 ovarian carcinoma. The mAb to TGF-α was most effective, and tumor lines releasing TGF-α were more sensitive than lines not releasing TGF-α. Stimulated by these findings we then performed pilot experiments in which mice with SW1 melanoma were injected with mAbs intraperitoneally or with a combination of the 2. A combination of anti-TGF-α and anti-PD-1 mAbs could cure mice with established tumor while single anti-TGF-α or anti-PD1 mAbs could not.