Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors

Curr Opin Immunol. 2015 Apr;33:1-8. doi: 10.1016/j.coi.2014.12.010. Epub 2015 Jan 7.

Abstract

Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Humans
  • Immunity, Innate / drug effects*
  • Immunotherapy
  • Molecular Targeted Therapy
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents