title: Novel immune check point inhibiting antibodies in cancer therapy-Opportunities and challenges.
abstract: Drug resistance of tumor cells to chemotherapy is limiting the therapeutic efficacy of most anticancer drugs and represents a major obstacle in medical oncology. However, treatment of various human malignancies with biologics, mostly monoclonal antibodies (mAbs), is not limited by such chemoresistance mechanisms. However, other resistance or evasion mechanisms limit the efficacy to anticancer therapeutic mAbs that engage tumor-associated antigens on the surface of the malignant cells. Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology. These mAbs do not directly attack the malignant cells as most anticancer mAbs; rather, they enhance the anti-tumor response of the immune system by targeting immune regulatory pathways. Three mAbs targeting immune checkpoint molecules are currently used in the clinic and new mAbs that target other potential inhibitory targets are being actively investigated. This therapeutic approach, while proving as highly beneficial for many patients, is prone to toxicities and side effects of an autoimmune nature. Defining suitable management algorithms and biomarkers that predict therapeutic effects and adverse toxicity are required to provide survival benefit for larger numbers of cancer patients. Overcoming these challenges, along with opportunities for new agents and combinatorial strategies are the main focus of immune checkpoint blockade research today.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Diesendruck
authors.affiliation: Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel. Electronic address: benhar@post.tau.ac.il.
authors.forename: Itai
authors.initials: I
authors.lastname: Benhar
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000494:pharmacology*; D015415:Biomarkers; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D024661:Potassium Channels, Inwardly Rectifying / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000074322:Antineoplastic Agents, Immunological; D015415:Biomarkers; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D061026:Programmed Cell Death 1 Receptor
keywords: CTLA4; Immune checkpoint inhibitors; Immune-related adverse events; PD-1 - PDL-1 axis; Therapeutic monoclonal antibodies