Tumor antigen (TA)-targeting monoclonal antibody (mAb)-based treatments are considered to be one of the most successful strategies in cancer therapy. Besides targeting TAs and inducing tumor cell death, such antibodies interact with immune cells through Fc-dependent mechanisms to induce adaptive memory immune responses. However, multiple inhibitory/immunosuppressive pathways can be induced by tumor cells to limit the establishment of an efficient antitumor response and consequently a sustained clinical response to TA-targeting mAbs. Here, we provide an overview on how TA-targeting mAbs in combination with conventional cancer therapies and/or inhibitors of key immunosuppressive pathways might represent promising approaches to achieve long-term tumor control.
Keywords: ADCC, antibody-dependent cell cytotoxicity; ADCP, antibody-dependent cell phagocytosis; B-NHL, B-cell non-Hodgkin's lymphoma; CDC, complement-dependent cytotoxicity; CTLA4, cytotoxic T-lymphocyte-associated protein 4; DC, dendritic cell; FDA, food and drug administration; FcRn, neonatal Fc receptor; HMGB1, high-mobility group box 1; ICD, immunologic cell death; IDO, indoleamine 2, 3-dioxygenase; IFNγ, interferon γ; MDSC, myeloid-derived suppressor cell; NK, natural killer; PD-1, programmed cell death 1; TA, tumor antigen; TA-targeting mAbs; Treg, regulatory T cell; combined therapies; immunomodulation; immunosuppressive pathways; mAb, monoclonal antibody; vaccine-like effects.