The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer

Br J Haematol. 2017 Oct;179(1):20-35. doi: 10.1111/bjh.14770. Epub 2017 May 30.

Abstract

CD25 (also termed IL2RA) forms one component of the high-affinity heterotrimeric interleukin 2 (IL2) receptor on activated T cells. Its affinity for IL2 and cellular function are tightly regulated and vary in different cell types. The high frequency of CD25 on the surface of many different haematological tumour cells is now well established and, apart from its prognostic significance, CD25 may be present on leukaemic stem cells and enable oncogenic signalling pathways in leukaemic cells. Additionally, high CD25 expression in activated circulating immune cells and Tregs is a factor that has already been exploited by IL2 immunotherapies for treatment of tumours and autoimmune disease. The relative clinical safety and efficacy of administering anti-CD25 radioimmunoconjugates and immunotoxins in various haematological tumour indications has been established and clinical trials of a novel CD25-directed antibody drug conjugate are underway.

Keywords: CD25; CD25-expressing malignancies; anti-CD25 targeted therapy; interleukin-2 receptor; regulatory T cells.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Immunomodulation / drug effects*
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors*
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Signal Transduction / drug effects
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Antibodies, Monoclonal
  • Immunologic Factors
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Interleukin-2