Limitations in the Design of Chimeric Antigen Receptors for Cancer Therapy

Cells. 2019 May 17;8(5):472. doi: 10.3390/cells8050472.

Abstract

Cancer therapy has entered a new era, transitioning from unspecific chemotherapeutic agents to increasingly specific immune-based therapeutic strategies. Among these, chimeric antigen receptor (CAR) T cells have shown unparalleled therapeutic potential in treating refractory hematological malignancies. In contrast, solid tumors pose a much greater challenge to CAR T cell therapy, which has yet to be overcome. As this novel therapeutic modality matures, increasing effort is being invested to determine the optimal structure and properties of CARs to facilitate the transition from empirical testing to the rational design of CAR T cells. In this review, we highlight how individual CAR domains contribute to the success and failure of this promising treatment modality and provide an insight into the most notable advances in the field of CAR T cell engineering.

Keywords: CAR T cell; adoptive cell therapy; chimeric antigen receptor; immunotherapy.

Publication types

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

MeSH terms

  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • CD8 Antigens / immunology
  • Cell Engineering / methods*
  • Gene Editing
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / therapy*
  • Protein Domains / immunology
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Chimeric Antigen / immunology*
  • Single-Chain Antibodies / immunology
  • Transgenes
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology

Substances

  • CD28 Antigens
  • CD3 Complex
  • CD3 antigen, zeta chain
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • Single-Chain Antibodies
  • TMIGD2 protein, human
  • TNFRSF9 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 9