Reorienting the immune system in the treatment of cancer by using anti-PD-1 and anti-PD-L1 antibodies

• Published in: Drug discovery today 2015-09, Vol.20 (9), p.1127-1134
• Main Authors: Borch, Troels H., Donia, Marco, Andersen, Mads H., Svane, Inge M.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; B7-H1 Antigen - immunology; Drug Synergism; Humans; Ipilimumab; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; Programmed Cell Death 1 Ligand 2 Protein - immunology; Programmed Cell Death 1 Receptor - immunology
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2015.07.003

•We review PD-1 pathway blockade in the context of immunotherapy of cancer.•PD-1 and its ligands are excellent targets in anti-cancer therapy.•Anti-PD-1 and anti-PD-L1 antibodies have shown promising clinical activity.•Two anti-PD-1 antibodies are FDA-approved for treatment of metastatic melanoma.•Combination therapy holds the promise of producing stronger anti-cancer effects. Physiologically, the programmed death 1 (PD-1) pathway is involved in limiting the killing of bystander cells during an infection and controlling autoimmunity. However, cancers exploit this system to avoid immune killing, and PD-1 ligand 1 and 2 (PD-L1 and PD-L2) expression on tumor cells, as well as PD-1 expression on tumor-infiltrating lymphocytes, have shown to be negative prognostic factors. Promising clinical results have been obtained by PD-1 pathway blockade in a range of cancers while still maintaining a manageable toxicity profile, and two anti-PD-1 antibodies are now approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma. As already shown with nivolumab and ipilimumab, the combination of PD-1 pathway blockade with other anticancer agents holds promise in the form of additive synergistic anticancer effects.