| Autor: |
Molly R. Braun, Anne C. Moore, Jonathan D. Lindbloom, Katherine A. Hodgson, Emery G. Dora, Sean N. Tucker |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Vaccines, Vol 12, Iss 9, p 955 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2076-393X |
| DOI: |
10.3390/vaccines12090955 |
| Popis: |
Therapeutic vaccination can harness the body’s cellular immune system to target and destroy cancerous cells. Several treatment options are available to eliminate pre-cancerous and cancerous lesions caused by human papillomaviruses (HPV), but may not result in a long-term cure. Therapeutic vaccination may offer an effective, durable, and minimally intrusive alternative. We developed mucosally delivered, recombinant, non-replicating human adenovirus type 5 (rAd5)-vectored vaccines that encode HPV16′s oncogenic proteins E6 and E7 alongside a molecular dsRNA adjuvant. The induction of antigen-specific T cells and the therapeutic efficacy of rAd5 were evaluated in a mouse model of HPV tumorigenesis where E6E7-transformed cells, TC-1, were implanted subcutaneously in C57BL/6 mice. After tumor growth, mice were treated intranasally with rAd5 vaccines expressing the wildtype form of E6E7 (rAd5-16/E6E7Wt) in combination with an anti-PD-1 antibody or isotype control. Animals treated with rAd5-16/E6E7Wt with and without anti-PD-1 had significant reductions in tumor volume and increased survival compared to controls. Further, animals treated with rAd5-16/E6E7Wt had increased CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) and produced a cytotoxic tumor microenvironment. In a second study, the immunogenicity of a non-transformative form of E6E7 (rAd5-16/E6E7Mu) and a vaccine encoding predicted T cell epitopes of E6E7 (rAd5-16/E6E7epi) were evaluated. These vaccines elicited significant reductions in TC-1 tumor volume and increased survival of animals. Antigen-specific CD8+ T effector memory cells were observed in the animals treated with E6E7-encoding rAd5, but not in the rAd5-empty group. The work described here demonstrates that this mucosal vaccination can be used therapeutically to elicit specific cellular immunity and further identifies a clinical candidate with great potential for the treatment and prevention of human cervical cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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