Synthetic Immunotherapy: Programming Immune Cells with Novel and Sophisticated Logic Capabilities

Research output: Contribution to journalReview articlepeer-review

Abstract

The development of chimeric antigen receptor (CAR) T cells began as a means toward specific yet modular therapies against cancer. Recent advancements in several CAR T cell therapies show the promise of cellular immunotherapy in cancer treatment. CAR T cell therapy is still immature, however, and improvements are needed to fully realize its curative potential. The approved CAR T cells are designed with simple logic capabilities; an antigen sensor that, when bound to the target antigen, triggers costimulation domains and native T cell activation. This single-type sensor and native activation design, although capable, also has severe limitations. Reliance on a single-type sensor leads to unwanted toxicity toward antigen-expressing normal tissues, and unmodulated activation leads to unwanted cytokine toxicity. Synthetic biology (SB) offers a powerful solution to these limitations: modular receptors with customizable sensors and output behaviors that enable higher Boolean logic. SB T cells already have shown incredible capabilities, such as multiple-antigen discrimination and improved persistence. In light of these results, cellular immunotherapy may already be branching into a new subfield that we term here as “synthetic immunotherapy.” Here we review the current logic capabilities of CAR T cells, the resulting limitations, and the engineering undertaken to address these issues. We then discuss several tools of SB and show how SB CAR T cells pave the way for synthetic immunotherapy.

Original languageEnglish (US)
Pages (from-to)560-571
Number of pages12
JournalTransplantation and Cellular Therapy
Volume28
Issue number9
DOIs
StatePublished - Sep 2022

Keywords

  • CAR T cell
  • Cell engineering
  • Cellular immunotherapy
  • Synthetic biology
  • Synthetic biology CAR T cell
  • Synthetic immunotherapy
  • Synthetic receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Medicine
  • Hematology
  • Cell Biology
  • Transplantation

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