表位
免疫疗法
癌症
人类白细胞抗原
人乳头瘤病毒
癌症免疫疗法
受体
医学
鉴定(生物学)
免疫学
情感(语言学)
抗原
病毒学
肿瘤科
计算生物学
生物
内科学
心理学
沟通
植物
作者
Chengjie Xiong,Lihong Huang,Hedan Kou,Chenwei Wang,Xiaomin Zhang,Hanli Sun,Shang-Yuan Liu,Bin Wu,Jingyao Li,Xiaoling Wang,Zibing Wang,Lin Chen
标识
DOI:10.1136/jitc-2022-004790
摘要
Background E6 and E7 oncoproteins are considered ideal antigens of T cell therapy for human papillomavirus (HPV)-related cancers. However, little is known about the epitopes of E6 and E7 presented by HLA-A*11:01, one of the most prevalent HLA types globally, especially in Asia. Methods We combined in silico and experimental approaches to identify endogenously processed HLA-A*11:01-restricted epitopes of HPV16 E6 and E7. The identified epitopes were then used to screen available T cell receptors (TCRs) from healthy donors through in vitro stimulation of peripheral blood mononuclear cells (PBMCs). Results E6 93-101 (TTLEQQYNK, TTL) and E7 89-97 (IVCPICSQK, IVC), two novel HLA-A*11:01-restricted T cell epitopes of HPV16, were identified to be endogenously presented on tumor cells. TTL- and IVC-specific TCRs were isolated from 11 healthy donors through in vitro stimulation of PBMC. The key TTL and IVC residues involved in TCR-pMHC interactions were mapped, and the consensus sequence was “xxLEQxYNK” and “xVxPIxxxK.” The TTL- and IVC-specific TCRs with high functional avidity were used to generate TCR-engineered T cells, specifically recognizing and killing corresponding tumor cell lines in vitro and in vivo. In addition, TTL and IVC-specific TCR-T cells also recognized and killed HPV16 + patient-derived organoids. Conclusions The HLA-A*11:01-restricted HPV16 E6/E7 epitopes and TCRs identified in this study may provide a new strategy for HPV-related cancer immunotherapy in HLA-A*11:01 + patients.
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