title: Immune Checkpoint inhibitors: An introduction to the next-generation cancer immunotherapy.
abstract: Activating the immune system to eliminate cancer cells and produce clinically relevant responses has been a long-standing goal of cancer research. Most promising therapeutic approaches to activating antitumor immunity include immune checkpoint inhibitors. Immune checkpoints are numerous inhibitory pathways hardwired in the immune system. They are critical for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues to minimize collateral tissue damage. Tumors regulate certain immune checkpoint pathways as a major mechanism of immune resistance. Because immune checkpoints are initiated by ligand-receptor interactions, blockade by antibodies provides a rational therapeutic approach. Although targeted therapies are clinically successful, they are often short-lived due to rapid development of resistance. Immunotherapies offer one notable advantage. Enhancing the cell-mediated immune response against tumor cells leads to generation of a long-term memory lymphocyte population patrolling the body to attack growth of any new tumor cells, thereby sustaining the therapeutic effects. Furthermore, early clinical results suggest that combination immunotherapies offer even more potent antitumor activity. This review is intended to provide an introduction to immune checkpoint inhibitors and discusses the scientific overview of cancer immunotherapy, mechanisms of the inhibitors, clinical pharmacology considerations, advances in combination therapies, and challenges in drug development.
authors.affiliation: Clinical Pharmacology, Immunomedics Inc., Morris Plains, NJ, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Lee
authors.affiliation: Clinical Pharmacology & Pharmacometrics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Clinical Pharmacology, Genentech Inc., San Francisco, CA, USA.
authors.forename: Srikumar
authors.initials: S
authors.lastname: Sahasranaman
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents
keywords: Biomarkers; Clinical Pharmacology (CPH); Immunopharmacology (IMM); Oncology (ONC); Pharmacodynamics (PDY)