| abstract |
The present invention is based on the promising discovery that targeted immunomodulating antibodies and fusion proteins can counteract or reverse immune tolerance of cancer cells. Cancer cells can escape elimination by chemotherapeutic agents or tumor-targeted antibodies through specific immunosuppressive mechanisms in the tumor microenvironment, and the ability of such cancer cells is recognized as immune tolerance. Such immunosuppressive mechanisms include immunosuppressive cytokines such as transforming growth factor beta (TGF-β) and regulatory T cells and / or immunosuppressive myeloid dendritic cells (DC). By combating tumor-induced immune tolerance, the present invention provides compositions and methods effective for cancer treatment, optionally in combination with another existing cancer treatment. The present invention provides a strategy to counteract tumor-induced immune tolerance and enhance the antitumor effect of chemotherapy by activating and depleting T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells. provide. |