Open AccessOvercoming Tumor-Induced Immune Suppression: From Relieving Inhibition to Providing Costimulation with T Cell Agonists
Author(s) -
Dana A. Emerson,
William L. Redmond
Publication year - 2018
Publication title -
biodrugs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.919
H-Index - 67
eISSN - 1179-190X
pISSN - 1173-8804
DOI - 10.1007/s40259-018-0277-2
Subject(s) - immune system , immunotherapy , cancer immunotherapy , immunology , receptor , tumor microenvironment , cytotoxic t cell , biology , monoclonal antibody , cancer research , antigen , t cell , immune checkpoint , antibody , in vitro , biochemistry
Recent advancements in T-cell biology and antibody engineering have opened doors to significant improvements in cancer immunotherapy. Initial success with monoclonal antibodies targeting key receptors that inhibit T-cell function such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-1) have demonstrated the potency of this new class of therapy, highlighted by long-term complete responses for metastatic cancers once thought incurable. However, only a subset of patients responds to checkpoint blockade because of a multitude of factors, including an immunosuppressive tumor microenvironment and the mutational burden of the cancer. Novel antibodies, as well as ligand-immunoglobulin fusion proteins that target costimulatory immune receptors, are being developed and tested in clinical trials to further enhance the anti-tumor immune response. Many of these costimulatory receptors are in the tumor necrosis factor receptor superfamily (TNFRSF) and are expressed on multiple immune cell types, including inhibitory cells. While TNFRSFs signal through common pathways, the outcome of targeting different receptors depends on the functional status of the cell types expressing the relevant receptors. In this review, we discuss the current state of targeted costimulatory immunotherapy.