Anti-PD-1 monoclonal antibody Cancer immunotherapy

Mechanistic studies to understand how immune checkpoint blockade induces regressions in several types of cancer have identified therapies that enhance tumor immunity as a treatment strategy. The programmed cell death protein 1 (hPD-1) receptor is a co-inhibitory receptor expressed by activated T lymphocytes. Anti-hPD-1 and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies potentiate immune responses by blocking the interaction between the PD-1 protein and one of its ligands (PD-L), thereby preventing activated cells from becoming anergic, while preserving antitumor immunological activity. Nivolumab, a fully human IgG(4) antibody that blocks this receptor, has been demonstrated to produce durable objective responses, particularly in patients with melanoma, renal cell cancer and non-small cell lung cancer, while exhibiting a better safety profile compared with similar agents acting upon other checkpoint receptors. Herewith, we review all available evidence to illustrate nivolumab's immunological mechanism of action, its pharmacokinetic/pharmacodynamic and safety profile, and preclinical and clinical trials to date with nivolumab alone or combined with other immunomodulators/chemotherapeutics.