PMID- 38410235 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240229 IS - 2219-6803 (Electronic) IS - 2218-676X (Print) IS - 2218-676X (Linking) VI - 13 IP - 1 DP - 2024 Jan 31 TI - Fusion of NY-ESO-1 epitope with heat shock protein 70 enhances its induced immune responses and antitumor activity against glioma in vitro. PG - 191-201 LID - 10.21037/tcr-23-1476 [doi] AB - BACKGROUND: Glioma is the most common tumor originating in the brain and is difficult to cure. New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising cancer testis antigen (CTA) for tumor immunotherapy, and heat shock proteins (HSPs) can promote the antigen presentation of chaperoned peptides. This study investigates the therapeutic potential of HSP70 and NY-ESO-1 epitope fusion protein for glioma. METHODS: Recombinant HSP70 protein was purified and fused to NY-ESO-1 epitope to generate HSP70/NY-ESO-1 p86-94. NY-ESO-1 expression was induced in U251 glioma cells via 5-Aza-2'-deoxycytidine (5-Aza-CdR) treatment. Dendritic cells (DCs) loaded with HSP70/NY-ESO-1 p86-94 or NY-ESO-1 protein stimulated NY-ESO-1-specific cytotoxic T lymphocytes (CTLs). The killing effect of NY-ESO-1 specific CTLs on U251 cells was detected by lactate dehydrogenase (LDH). RESULTS: 5-Aza-CdR successfully induced NY-ESO-1 expression in U251 cells. NY-ESO-1-stimulated CTLs lysed more significantly with NY-ESO-1-positive U251 cells than with NY-ESO-1-negative cells. The immune response stimulated by a DC-based vaccine of HSP70/NY-ESO-1 p86-94 fusion protein was significantly enhanced compared with that induced by NY-ESO-1 alone. CONCLUSIONS: These findings indicate that the HSP70/NY-ESO-1 p86-94 may significantly enhance CTLs-mediated cytotoxicity and targeting ability against NY-ESO-1-expressing tumors in vitro. 5-Aza-CdR treatment with HSP70 binding to tumor antigen is a new strategy for immunotherapy of the tumors with poor CTA expression. CI - 2024 Translational Cancer Research. All rights reserved. FAU - Chen, Yuqing AU - Chen Y AD - Department of Pathology and Institute of Oncology, School of Basic Medical Science, Fujian Medical University, Fuzhou, China. AD - Diagnostical Pathology Center, Fujian Medical University, Fuzhou, China. FAU - Zheng, Lin AU - Zheng L AD - Department of Pathology and Institute of Oncology, School of Basic Medical Science, Fujian Medical University, Fuzhou, China. AD - Diagnostical Pathology Center, Fujian Medical University, Fuzhou, China. FAU - Hua, Wenxi AU - Hua W AD - Department of Pathology and Institute of Oncology, School of Basic Medical Science, Fujian Medical University, Fuzhou, China. AD - Diagnostical Pathology Center, Fujian Medical University, Fuzhou, China. FAU - Wang, Jie AU - Wang J AD - Department of Pathology and Institute of Oncology, School of Basic Medical Science, Fujian Medical University, Fuzhou, China. AD - Diagnostical Pathology Center, Fujian Medical University, Fuzhou, China. FAU - Chen, Lihong AU - Chen L AD - Department of Pathology and Institute of Oncology, School of Basic Medical Science, Fujian Medical University, Fuzhou, China. AD - Diagnostical Pathology Center, Fujian Medical University, Fuzhou, China. FAU - Huang, Aimin AU - Huang A AD - Department of Pathology and Institute of Oncology, School of Basic Medical Science, Fujian Medical University, Fuzhou, China. AD - Diagnostical Pathology Center, Fujian Medical University, Fuzhou, China. FAU - Zhang, Wenmin AU - Zhang W AD - Department of Pathology and Institute of Oncology, School of Basic Medical Science, Fujian Medical University, Fuzhou, China. AD - Diagnostical Pathology Center, Fujian Medical University, Fuzhou, China. LA - eng PT - Journal Article DEP - 20240119 PL - China TA - Transl Cancer Res JT - Translational cancer research JID - 101585958 PMC - PMC10894325 OTO - NOTNLM OT - 5-Aza-2'-deoxycytidine (5-Aza-CdR) OT - New York esophageal squamous cell carcinoma 1 (NY-ESO-1) OT - dendritic cell (DC) OT - glioma OT - heat shock protein 70 (HSP70) COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1476/coif). All authors report that the work was supported by grants from National Natural Science Foundation of China (No. 81472830) and Natural Science Foundation of Fujian Province (Nos. 2018J01835, 2022J01202). The authors have no other conflicts of interest to declare. EDAT- 2024/02/27 06:44 MHDA- 2024/02/27 06:45 PMCR- 2024/01/31 CRDT- 2024/02/27 03:36 PHST- 2023/08/15 00:00 [received] PHST- 2023/11/29 00:00 [accepted] PHST- 2024/02/27 06:45 [medline] PHST- 2024/02/27 06:44 [pubmed] PHST- 2024/02/27 03:36 [entrez] PHST- 2024/01/31 00:00 [pmc-release] AID - tcr-13-01-191 [pii] AID - 10.21037/tcr-23-1476 [doi] PST - ppublish SO - Transl Cancer Res. 2024 Jan 31;13(1):191-201. doi: 10.21037/tcr-23-1476. Epub 2024 Jan 19.