CAR T Cell Therapy for Neuroblastoma

Front Immunol. 2018 Oct 16:9:2380. doi: 10.3389/fimmu.2018.02380. eCollection 2018.

Abstract

Patients with high risk neuroblastoma have a poor prognosis and survivors are often left with debilitating long term sequelae from treatment. Even after integration of anti-GD2 monoclonal antibody therapy into standard, upftont protocols, 5-year overall survival rates are only about 50%. The success of anti-GD2 therapy has proven that immunotherapy can be effective in neuroblastoma. Adoptive transfer of chimeric antigen receptor (CAR) T cells has the potential to build on this success. In early phase clinical trials, CAR T cell therapy for neuroblastoma has proven safe and feasible, but significant barriers to efficacy remain. These include lack of T cell persistence and potency, difficulty in target identification, and an immunosuppressive tumor microenvironment. With recent advances in CAR T cell engineering, many of these issues are being addressed in the laboratory. In this review, we summarize the clinical trials that have been completed or are underway for CAR T cell therapy in neuroblastoma, discuss the conclusions and open questions derived from these trials, and consider potential strategies to improve CAR T cell therapy for patients with neuroblastoma.

Keywords: CAR T cells; adoptive T cell therapy; clinical trials; immunotherapy; neuroblastoma; pediatric oncology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Animals
  • Antigens, Neoplasm / immunology
  • Clinical Trials as Topic
  • Genetic Engineering
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Neuroblastoma / immunology*
  • Neuroblastoma / pathology
  • Neuroblastoma / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism*
  • T-Cell Antigen Receptor Specificity / genetics
  • T-Cell Antigen Receptor Specificity / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen