Challenges and opportunities of allogeneic donorderived CAR T cells

Yinmeng Yang, Elad Jacoby, Terry J. Fry*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Purpose of review As T cells engineered with chimeric antigen receptors (CARs) are entering advanced phases of clinical trial testing with promising results, the potential implications of use in an allogeneic environment are emerging as an important consideration. This review discusses the use of allogeneic CAR therapy, the potential effects of T-cell receptor (TCR) signaling on CAR T-cell efficacy, and the potential for TCR elimination to generate an off-the-shelf product. Recent findings The majority of preclinical and clinical data regarding allogeneic T cells are focused on safety of their use given the potential for graft-versus-host disease (GVHD) mediated by the T-cell receptor expressed with the introduced CAR. Recent clinical trials using donor-derived CAR T cells are using either rigorous patient selection or T-cell selection (such as enrichment for virus-specific T cells). Although no GVHD has been reported, the efficacy of the allogeneic CAR treatment needs to be optimized. Several preclinical models limit allogeneic CAR-driven GVHD by utilizing memory T-cell selection, virus-specific T cells, gene-editing techniques, or suicide gene engineering. Summary In the allogeneic environment, the potential effects of TCR signaling on the efficacy of CAR could affect the clinical responses with the use of donor-derived CAR T cells. Better understanding of the functionality of donor-derived T cells for therapy is essential for the development of universal effector cells for CAR therapy.

Original languageEnglish
Pages (from-to)509-515
Number of pages7
JournalCurrent Opinion in Hematology
Volume22
Issue number6
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Adoptive immunotherapy
  • Allogeneic hematopoietic stem cell transplantation
  • Chimeric antigen receptors
  • Donor derived
  • Graft-versus-host disease

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