Novel immunotherapies for hematologic malignancies

Immunol Rev. 2015 Jan;263(1):90-105. doi: 10.1111/imr.12245.

Abstract

The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise novel strategies that exploit the patient's immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematologic malignancies, including (i) conventional monoclonal therapies like rituximab; (ii) engineered monoclonal antibodies called bispecific T-cell engagers; (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4, and IDO); and (iv) adoptive cell transfer therapy with T cells engineered to express chimeric antigen receptors or T-cell receptors. We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients.

Keywords: adoptive T-cell transfer therapy; allogeneic hematopoietic stem cell transplantation; bispecific T-cell engagers; gene transfer; immune checkpoint modulators; monoclonal antibodies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunotherapy / methods*
  • Lymphocyte Activation / drug effects
  • Protein Engineering
  • Receptor Cross-Talk / drug effects
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins / therapeutic use*
  • Signal Transduction / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / physiology
  • T-Lymphocytes / transplantation
  • Translational Medical Research
  • Tumor Escape

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins