Engineering Tolerance toward Allogeneic CAR-T Cells by Regulation of MHC Surface Expression with Human Herpes Virus-8 Proteins

Xiaomei Wang, Fabricio G. Cabrera, Kelly L. Sharp, David M. Spencer, Aaron E. Foster, J. Henri Bayle

Research output: Contribution to journalArticle

Abstract

Implantation of allogeneic, off-the-shelf chimeric antigen receptor (CAR)-based anti-cancer cell therapies may reduce the cost and variation in cell quality of autologous approaches but suffers from reduced cell persistence from host immune rejection. Wang et al. report the engineering of T cells to express membrane-tethered E3 ubiquitin ligases K3 and K5 derived from HHV8. K3 and K5 target MHC and MIC-A/B complexes for lysosomal degradation, reducing allogeneic T and NK cell recognition while maintaining the anti-tumor potency of CAR-T cells.

Original languageEnglish (US)
Pages (from-to)718-733
Number of pages16
JournalMolecular Therapy
Volume29
Issue number2
DOIs
StatePublished - Feb 3 2021

Keywords

  • CAR-T cell
  • HHV8
  • MARCH proteins
  • OTS
  • allogeneic cell therapy
  • iMC
  • immune evasion
  • off-the-shelf cell therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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