首页|Engineering immunosuppressive drug-resistant armored(IDRA)SARS-CoV-2 T cells for cell therapy

Engineering immunosuppressive drug-resistant armored(IDRA)SARS-CoV-2 T cells for cell therapy

扫码查看
原文链接
  • 万方数据
Solid organ transplant(SOT)recipients receive immunosuppressive drugs(ISDs)and are susceptible to developing severe COVID-19.Here,we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group of SOT patients(n=136)treated with different ISDs.We demonstrate that a combination of a calcineurin inhibitor(CNI),mycophenolate mofetil(MMF),and prednisone(Pred)treatment regimen strongly suppressed the mRNA vaccine-induced Spike-specific cellular response.Such defects have clinical consequences because the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection.To then compensate for the T-cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients,we describe production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T-cell receptor(TCR)-T cells engineered using the mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta,Delta,Gamma,and Omicron variants.This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.

T cell therapyTransplantationSARS-CoV-2Immunosuppressive drug resistant T cells

Qi Chen、Adeline Chia、Shou Kit Hang、Amy Lim、Wee Kun Koh、Yanchun Peng、Fei Gao、Jili Chen、Zack Ho、Lu-En Wai、Kamini Kunasegaran、Anthony Tanoto Tan、Nina Le Bert、Chiew Yee Loh、Yun Shan Goh、Laurent Renia、Tao Dong、Anantharaman Vathsala、Antonio Bertoletti

展开 >

Emerging Infectious Disease Program,Duke-NUS Medical School,Singapore,Singapore

National University Centre for Organ Transplantation,National University Hospital,Singapore,Singapore

MRC Human Immunology Unit,MRC Weatherall Institute of Molecular Medicine,Radcliffe Department of Medicine,University of Oxford,Oxford,UK

Lion TCR Pte Ltd,Singapore,Singapore

A*STAR ID labs,Agency for Science,Technology and Research,Singapore,Singapore

Lee Kong Chian School of Medicine,Nanyang Technological University,Singapore,Singapore

Department of Medicine,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,Singapore

Singapore Immunology Network,A*STAR,Singapore,Singapore

展开 >

Singapore Ministry of Health's National Medical Research CouncilSingapore Ministry of Health's National Medical Research CouncilA*ccelerate GAP-funded project from the Agency of Science,Technology and Research(A*STAR)Singapore National Medical Research Council COVID-19 Research Funda Startup University Grant from the Ministry of Education(Singapore)a Career Development Fund award by A*STAR

MOH-000019MOH-StaR17Nov-001ACCL/19-GAP064-R20H-HCOVID19RF-011SC35/22-805100

2023

10.1038/s41423-023-01080-3

中国免疫学杂志(英文版)
中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI
影响因子：0.731
ISSN：1672-7681
年,卷(期)：2023.20(11)
  • 47