Therapeutic human papillomavirus (HPV) vaccines targeting E6 and/or E7 antigens represent an opportunity to control HPV-associated lesions. We have previously generated several therapeutic DNA vaccines targeting HPV-16 E7 antigen and generated significant antitumor effects. Since regulatory T cells (Tregs) play an important role in suppressing immune responses against tumors by immunotherapy, such as DNA vaccines, we tested if the therapeutic effects of a DNA vaccine encoding E7 linked to heat shock protein 70 (Hsp70) can be improved by a strategy to deplete Tregs using a anti-CD25 monoclonal antibody (PC61) in vaccinated mice. We found that administration of PC61 prior to vaccination with E7/Hsp70 DNA was capable of generating higher levels of E7-specific CD8(+) T cells compared to the control antibody, leading to significantly improved therapeutic and long-term protective antitumor effects against an E7-expressing tumor, TC-1. Thus, a strategy to deplete CD4(+)CD25(+) Tregs in conjunction with therapeutic tumor antigen-specific DNA vaccine may represent a potentially promising approach to control tumor. The clinical implications of our study are discussed.

2003-10-01·Molecular Therapy1区 · 医学

Boosting with recombinant vaccinia increases HPV-16 E7-Specific T cell precursor frequencies and antitumor effects of HPV-16 E7-Expressing sindbis virus replicon particles

1区 · 医学

Article

作者: Tae Woo Kim ; Jeremy Juang ; Ken Yu Lin ; Chien Fu Hung ; Liangmei He ; Cheng Tao Lin ; T. C. Wu

Immunotherapy using the heterologous prime-boost regimen has emerged as an attractive approach for generating antigen-specific T-cell-mediated immune responses against tumors and infectious diseases. We have previously linked the Mycobacterium tuberculosis heat-shock protein 70 (HSP70) to the HPV-16 E7 antigen creating a chimera, E7/HSP70. We found that nucleic acid vaccines encoding E7/HSP70 can generate strong antitumor immunity. Recently, replication-defective Sindbis virus replicon particle vaccines have been considered as an important vector system for vaccine development. In this study, we assessed whether the combination of E7/HSP70 Sindbis virus replicon particles (SINrep5-E7/HSP70) and E7/HSP70 vaccinia (Vac-E7/HSP70) can further enhance E7-specific immune responses using sequential vaccination. We found that priming with SINrep5-E7/HSP70 and boosting with Vac-E7/HSP70 generated the highest number of E7-specific CD8(+) T cells and best antitumor effect compared to other combinations. Moreover, our data showed that at the dosage and route of immunization used in this study, mice treated with the Sindbis virus replicon particle prime-vaccinia boost regimen generated stronger antitumor responses compared to mice treated with the DNA prime-vaccinia boost vaccine regimen. Our results encourage the use of the Sindbis virus replicon particle prime-vaccinia boost regimen in future clinical trials.

100 项与 HPV 16 E7/HSP70 fused DNA vaccine(The Johns Hopkins University) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
卵巢癌	临床2期	-	The Johns Hopkins University	-
头颈部鳞状细胞癌	临床2期	-	The Johns Hopkins University	-
子宫颈发育不良	临床2期	-	The Johns Hopkins University	-