Reference Database

HLA-class II restricted TCR targeting human papillomavirus type 18 E7 induces solid tumor remission in mice.
Long, Jianting
Chen, Xihe
He, Mian
Ou, Shudan
Zhao, Yunhe
Yan, Qingjia
Ma, Minjun
Chen, Jingyu
Qin, Xuping
Zhou, Xiangjun
Chu, Junjun
Han, Yanyan
Nat Commun 2024 Mar 13;15(1): 2271

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 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.

Forward to a friend