PMID- 38480731
OWN - NLM
STAT- MEDLINE
DCOM- 20240315
LR  - 20240316
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 15
IP  - 1
DP  - 2024 Mar 13
TI  - HLA-class II restricted TCR targeting human papillomavirus type 18 E7 induces 
      solid tumor remission in mice.
PG  - 2271
LID - 10.1038/s41467-024-46558-4 [doi]
LID - 2271
AB  - T cell receptor (TCR)-engineered T cell therapy is a promising potential 
      treatment for solid tumors, with preliminary efficacy demonstrated in clinical 
      trials. However, obtaining clinically effective TCR molecules remains a major 
      challenge. We have developed a strategy for cloning tumor-specific TCRs from 
      long-term surviving patients who have responded to immunotherapy. Here, we report 
      the identification of a TCR (10F04), which is human leukocyte antigen 
      (HLA)-DRA/DRB1*09:01 restricted and human papillomavirus type 18 (HPV18) 
      E7(84-98) specific, from a multiple antigens stimulating cellular therapy (MASCT) 
      benefited metastatic cervical cancer patient. Upon transduction into human T 
      cells, the 10F04 TCR demonstrated robust antitumor activity in both in vitro and 
      in vivo models. Notably, the TCR effectively redirected both CD4(+) and CD8(+) T 
      cells to specifically recognize tumor cells and induced multiple cytokine 
      secretion along with durable antitumor activity and outstanding safety profiles. 
      As a result, this TCR is currently being investigated in a phase I clinical trial 
      for treating HPV18-positive cancers. This study provides an approach for 
      developing safe and effective TCR-T therapies, while underscoring the potential 
      of HLA class II-restricted TCR-T therapy as a cancer treatment.
CI  - (c) 2024. The Author(s).
FAU - Long, Jianting
AU  - Long J
AD  - Department of Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, PR China.
FAU - Chen, Xihe
AU  - Chen X
AD  - HRYZ Biotech Co., Guangzhou, PR China.
FAU - He, Mian
AU  - He M
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun 
      Yat-sen University, Guangzhou, PR China.
FAU - Ou, Shudan
AU  - Ou S
AD  - HRYZ Biotech Co., Guangzhou, PR China.
FAU - Zhao, Yunhe
AU  - Zhao Y
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun 
      Yat-sen University, Guangzhou, PR China.
FAU - Yan, Qingjia
AU  - Yan Q
AD  - HRYZ Biotech Co., Guangzhou, PR China.
FAU - Ma, Minjun
AU  - Ma M
AD  - HRYZ Biotech Co., Guangzhou, PR China.
FAU - Chen, Jingyu
AU  - Chen J
AD  - Department of Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, PR China.
FAU - Qin, Xuping
AU  - Qin X
AD  - Department of Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, PR China.
FAU - Zhou, Xiangjun
AU  - Zhou X
AD  - HRYZ Biotech Co., Guangzhou, PR China.
FAU - Chu, Junjun
AU  - Chu J
AUID- ORCID: 0000-0002-4916-5506
AD  - HRYZ Biotech Co., Guangzhou, PR China. chujunjun@shhryz.com.
FAU - Han, Yanyan
AU  - Han Y
AUID- ORCID: 0000-0002-1996-0138
AD  - HRYZ Biotech Co., Guangzhou, PR China. hanyanyan@shhryz.com.
LA  - eng
PT  - Journal Article
DEP - 20240313
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Female
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Human papillomavirus 18/metabolism
MH  - CD8-Positive T-Lymphocytes
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - *Uterine Cervical Neoplasms/therapy
MH  - HLA Antigens
PMC - PMC10937927
COIS- X.C., S.O., Q.Y., M.M., X.Z., J.C., and Y.H. are employees of HRYZ Biotech Co. 
      All other co-authors declare no competing interests.
EDAT- 2024/03/14 06:46
MHDA- 2024/03/15 06:43
PMCR- 2024/03/13
CRDT- 2024/03/14 00:57
PHST- 2023/07/20 00:00 [received]
PHST- 2024/03/01 00:00 [accepted]
PHST- 2024/03/15 06:43 [medline]
PHST- 2024/03/14 06:46 [pubmed]
PHST- 2024/03/14 00:57 [entrez]
PHST- 2024/03/13 00:00 [pmc-release]
AID - 10.1038/s41467-024-46558-4 [pii]
AID - 46558 [pii]
AID - 10.1038/s41467-024-46558-4 [doi]
PST - epublish
SO  - Nat Commun. 2024 Mar 13;15(1):2271. doi: 10.1038/s41467-024-46558-4.