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B cells transduced with HPV16 E6/E7-expressing adenoviral vector can efficiently induce CTL-dependent anti-tumor immunity

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Background: Human papillomavirus (HPV) infection is responsible for cervical cancer, a common cancer in women. Since HPV infection and cancer development are controlled by the host immune system, immunotherapy against HPV can be helpful in preventing or treating HPV-associated cervical cancer. Two oncoproteins of HPV16, E6 and E7, are promising targets for immunotherapy against cervical cancer, because they are constitutively expressed in cervical cancer. Methods: Since cellular vaccines using B cells as well as dendritic cells offer an efficient approach to cancer immunotherapy, we opted to use B cells. We evaluated the immunogenicity and anti-tumor effects of a B cell vaccine transduced with HPV16 E6/E7-expressing adenovirus. Results: Vaccination with HPV16 E6/E7-transduced B cells induced E6/E7-specific $CD8^+$ T cell-dependent immune responses and generated anti-tumor effects against E6/E7-expressing TC-1 tumor. The anti-tumor effect induced by this B cell vaccine was similar to that elicited by DC vaccine, showing that B cells can be used as an alternative to dendritic cells for cellular vaccines. Conclusion: Thisstudy has shown the feasibility of using B cells as immunogenic APCs and the potential for developing prophylactic and therapeutic vaccines against HPV-associated cervical cancer using a B cell vaccine transduced with adenovirus expressing HPV16 E6/E7.

Abstract

Background: Human papillomavirus (HPV) infection is responsible for cervical cancer, a common cancer in women. Since HPV infection and cancer development are controlled by the host immune system, immunotherapy against HPV can be helpful in preventing or treating HPV-associated cervical cancer. Two oncoproteins of HPV16, E6 and E7, are promising targets for immunotherapy against cervical cancer, because they are constitutively expressed in cervical cancer. Methods: Since cellular vaccines using B cells as well as dendritic cells offer an efficient approach to cancer immunotherapy, we opted to use B cells. We evaluated the immunogenicity and anti-tumor effects of a B cell vaccine transduced with HPV16 E6/E7-expressing adenovirus. Results: Vaccination with HPV16 E6/E7-transduced B cells induced E6/E7-specific $CD8^+$ T cell-dependent immune responses and generated anti-tumor effects against E6/E7-expressing TC-1 tumor. The anti-tumor effect induced by this B cell vaccine was similar to that elicited by DC vaccine, showing that B cells can be used as an alternative to dendritic cells for cellular vaccines. Conclusion: Thisstudy has shown the feasibility of using B cells as immunogenic APCs and the potential for developing prophylactic and therapeutic vaccines against HPV-associated cervical cancer using a B cell vaccine transduced with adenovirus expressing HPV16 E6/E7.

관련 논문AI추천

Immunization with Adenoviral Vectors Carrying Recombinant IL-12 and E7 Enhanced the Antitumor Immunity against Human Papillomavirus 16-associated TumorByoung Don Han, Do Gang Kim, Eun Kyung Park, Heung Jae Chun, Hyun Sun Jin, Jeong Im Sin, Joon Mo Lee, Su Mi Bae, Sung Eun NamKoong, Woong Shick Ahn, Young Wook Kim대한암학회 · Cancer Research and Treatment2005 · 제37권 제1호HPV 16-E7 종양백신과 IL-12에 의한 항종양 면역능의 유도김도강, 김용완, 김종국, 박은경, 배수미, 안웅식, 윤주희, 윤철구, 이준모, 진태형, 최미나, 허승원, 남궁성은대한산부인과학회 · Obstetrics & Gynecology Science2003 · 제46권 제12호Oral Administration of Poly-Gamma-Glutamic Acid Significantly Enhances the Antitumor Effect of HPV16 E7-Expressing Lactobacillus casei in a TC-1 Mouse Model김은진, 부하령, 성문희, 양지현한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2019 · 제29권 제9호Adenovirus Vectors: Excellent Tools for Vaccine Development장준대한면역학회 · Immune Network2021 · 제21권 제1호T-Cells Modified with CD70 as an Alternative Cellular Vaccine for Antitumor Immunity김태규, 손현정, 신아리, 이상은, 조현일대한암학회 · Cancer Research and Treatment2020 · 제52권 제3호Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer김미현, 박민호, 양덕환, 윤정한, 이윤경, 이제중, 이현주, 임미선, 장윤영, 장재홍, 홍철이, Chun-Ji Jin, Than Nhan Nguyen Pham, Truc Anh Nguyen Thi대한암학회 · Cancer Research and Treatment2011 · 제43권 제1호

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