Boilesen, Ditte Rahbaek and Neckermann, Patrick and Willert, Torsten and Mueller, Mikkel Dons and Schroedel, Silke and Pertl, Cordula and Thirion, Christian and Asbach, Benedikt and Wagner, Ralf and Holst, Peter Johannes (2023) Efficacy and Synergy with Cisplatin of an Adenovirus Vectored Therapeutic E1E2E6E7 Vaccine against HPV Genome-Positive C3 Cancers in Mice. CANCER IMMUNOLOGY RESEARCH, 11 (2). pp. 261-275. ISSN 2326-6066, 2326-6074
Full text not available from this repository. (Request a copy)Abstract
Human papillomavirus (HPV) infections are the main cause of cervical and oropharyngeal cancers. As prophylactic vaccines have no curative effect, an efficient therapy would be highly desired. Most therapeutic vaccine candidates target only a small subset of HPV regulatory proteins, namely, E6 and E7, and are therefore restricted in the breadth of their immune response. However, research has suggested E1 and E2 as promising targets to fight HPV+ cancer. Here, we report the design of adenoviral vectors efficiently expres-sing HPV16 E1 and E2 in addition to transformation-deficient E6 and E7. Vaccination elicited vigorous CD4+ and CD8+ T-cell responses against all encoded HPV16 proteins in outbred mice and against E1 and E7 in C57BL/6 mice. Therapeutic vaccination of C3 tumor-bearing mice led to significantly reduced tumor growth and enhanced survival for both small and established tumors. Tumor biopsies revealed increased numbers of tumor-infiltrating CD8+ T cells in treated mice. Cisplatin enhanced the effect of therapeutic vaccination, accompanied by enhanced infiltration of dendritic cells into the tumor. CD8+ T cells were identified as effector cells in T-cell depletion assays, seemingly under regulation by FoxP3+CD4+ regulatory T cells. Finally, therapeutic vaccina-tion with Ad-Ii-E1E2E6E7 exhibited significantly enhanced sur-vival compared with vaccination with two peptides each harboring a known E6/E7 epitope. We hypothesize that this difference could be due to the induction of additional T-cell responses against E1. These results support the use of this novel vaccine candidate targeting an extended set of antigens (Ad-Ii-E1E2E6E7), in com-bination with cisplatin, as an advanced strategy to combat HPV+ cancers.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CANCER; NEURAL-NETWORKS; CELLS; INTEGRATION; CARCINOMA; RESPONSES; TUMORS; MOUSE; HEAD; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Mar 2024 09:28 |
| Last Modified: | 10 Mar 2024 09:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59511 |
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