HLA-class II restricted TCR targeting human papillomavirus type 18 E7 induces solid tumor remission in mice

Jianting Long, Xihe Chen, Mian He, Shudan Ou, Yunhe Zhao, Qingjia Yan, Minjun Ma, Jingyu Chen, Xuping Qin, Xiangjun Zhou, Junjun Chu () and Yanyan Han ()
Additional contact information
Jianting Long: Cancer Center, The First Affiliated Hospital, Sun Yat-sen University
Xihe Chen: HRYZ Biotech Co.
Mian He: The First Affiliated Hospital, Sun Yat-sen University
Shudan Ou: HRYZ Biotech Co.
Yunhe Zhao: The First Affiliated Hospital, Sun Yat-sen University
Qingjia Yan: HRYZ Biotech Co.
Minjun Ma: HRYZ Biotech Co.
Jingyu Chen: Cancer Center, The First Affiliated Hospital, Sun Yat-sen University
Xuping Qin: Cancer Center, The First Affiliated Hospital, Sun Yat-sen University
Xiangjun Zhou: HRYZ Biotech Co.
Junjun Chu: HRYZ Biotech Co.
Yanyan Han: HRYZ Biotech Co.

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract 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) E784-98 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46558-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46558-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-46558-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().