T cell-based targeted immunotherapies for patients with multiple myeloma

Int J Cancer. 2015 Apr 15;136(8):1751-68. doi: 10.1002/ijc.29190. Epub 2014 Sep 19.

Abstract

Despite high-dose chemotherapy followed by autologs stem-cell transplantation as well as novel therapeutic agents, multiple myeloma (MM) remains incurable. Following the general trend towards personalized therapy, targeted immunotherapy as a new approach in the therapy of MM has emerged. Better progression-free survival and overall survival after tandem autologs/allogeneic stem cell transplantation suggest a graft versus myeloma effect strongly supporting the usefulness of immunological therapies for MM patients. How to induce a powerful antimyeloma effect is the key issue in this field. Pivotal is the definition of appropriate tumor antigen targets and effective methods for expansion of T cells with clinical activity. Besides a comprehensive list of tumor antigens for T cell-based approaches, eight promising antigens, CS1, Dickkopf-1, HM1.24, Human telomerase reverse transcriptase, MAGE-A3, New York Esophageal-1, Receptor of hyaluronic acid mediated motility and Wilms' tumor gene 1, are described in detail to provide a background for potential clinical use. Results from both closed and on-going clinical trials are summarized in this review. On the basis of the preclinical and clinical data, we elaborate on three encouraging therapeutic options, vaccine-enhanced donor lymphocyte infusion, chimeric antigen receptors-transfected T cells as well as vaccines with multiple antigen peptides, to pave the way towards clinically significant immune responses against MM.

Keywords: clinical trials; genetic engineering; immunotherapy; multiple myeloma; tumor antigens.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Clinical Trials as Topic
  • Humans
  • Immunotherapy / methods
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / therapy*
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm