Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities

Annu Rev Immunol. 2017 Apr 26:35:229-253. doi: 10.1146/annurev-immunol-051116-052302.


The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

Keywords: T cells; chimeric antigen receptors; engineered immune cells; immunotherapy; synthetic Notch; synthetic biology.

Publication types

  • Review

MeSH terms

  • Allergy and Immunology*
  • Animals
  • Cancer Vaccines / immunology*
  • Genetic Engineering
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Recombinant Fusion Proteins / genetics
  • Synthetic Biology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation


  • Cancer Vaccines
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins