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

doi:10.1016/j.ymthe.2020.10.019

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 journal › Article › peer-review

11 Scopus citations

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 language	English (US)
Pages (from-to)	718-733
Number of pages	16
Journal	Molecular Therapy
Volume	29
Issue number	2
DOIs	https://doi.org/10.1016/j.ymthe.2020.10.019
State	Published - 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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10.1016/j.ymthe.2020.10.019

Cite this

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

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.",

keywords = "CAR-T cell, HHV8, MARCH proteins, OTS, allogeneic cell therapy, iMC, immune evasion, off-the-shelf cell therapy",

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doi = "10.1016/j.ymthe.2020.10.019",

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AU - Cabrera, Fabricio G.

AU - Sharp, Kelly L.

AU - Spencer, David M.

AU - Foster, Aaron E.

AU - Bayle, J. Henri

PY - 2021/2/3

Y1 - 2021/2/3

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AB - 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.

KW - CAR-T cell

KW - HHV8

KW - MARCH proteins

KW - OTS

KW - allogeneic cell therapy

KW - iMC

KW - immune evasion

KW - off-the-shelf cell therapy

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

Abstract

Keywords

ASJC Scopus subject areas

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