Development of immuno-oncology drugs - from CTLA4 to PD1 to the next generations

Nat Rev Drug Discov. 2016 Apr;15(4):235-47. doi: 10.1038/nrd.2015.35. Epub 2016 Mar 11.

Abstract

Since the regulatory approval of ipilimumab in 2011, the field of cancer immunotherapy has been experiencing a renaissance. This success is based on progress in both preclinical and clinical science, including the development of new methods of investigation. Immuno-oncology has become a sub-specialty within oncology owing to its unique science and its potential for substantial and long-term clinical benefit. Immunotherapy agents do not directly attack the tumour but instead mobilize the immune system - this can be achieved through various approaches that utilize adaptive or innate immunity. Therefore, immuno-oncology drug development encompasses a broad range of agents, including antibodies, peptides, proteins, small molecules, adjuvants, cytokines, oncolytic viruses, bi-specific molecules and cellular therapies. This Perspective summarizes the recent history of cancer immunotherapy, including the factors that led to its success, provides an overview of novel drug-development considerations, summarizes three generations of immunotherapies that have been developed since 2011 and, thus, illustrates the breadth of opportunities these new generations of immunotherapies represent.

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • CTLA-4 Antigen / immunology
  • Humans
  • Immunity / drug effects*
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Ipilimumab
  • Medication Therapy Management / trends
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Programmed Cell Death 1 Receptor / immunology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • CTLA-4 Antigen
  • Ipilimumab
  • Programmed Cell Death 1 Receptor
  • tremelimumab