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bioRxiv · 10.1101/2024.03.11.584519

Elimination of human papillomavirus 16-induced tumors by a mucosal rAd5 therapeutic vaccination in a pre-clinical study

Braun, M. R.·Lindbloom, J. D.·Moore, A. C.·Hodgson, K. A.·Dora, E. G.·Tucker, S. N.
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Abstract

Therapeutic vaccination can harness the bodys cellular immune system to target and destroy cancerous cells. Several invasive treatments are currently used to eliminate cancerous lesions caused by human papillomaviruses (HPV), however therapeutic vaccination may offer and effective and minimally intrusive alternative. We have developed recombinant, non-replicating human adenovirus type 5 (rAd5) vaccines that encode the HPV16 oncogenic proteins E6 and E7 alongside a molecular dsRNA adjuvant. The potency of these vaccines were examined in a mouse model of HPV tumorigenesis where E6E7-expressing and transformed cells were implanted subcutaneously into C57BL/6 mice. After tumor growth, mice were treated via intranasal administration with E6E7-encoding rAd5 vaccines expressing either a mutant form of E6E7 (rAd5-16/E6E7m), or predicted T cell epitopes of E6E7 (rAd5-16/E6E7epitopes). Animals receiving therapeutic treatments of rAd5-16/E6E7m and rAd5-16/E6E7epitopes had significant reductions in tumor volume and increased survival compared to animals treated with an empty rAd5 or left untreated. Further, antigen-specific CD8+ T effector memory cells (TEM) were observed in the animals treated with E6E7-encoding rAd5, but not in rAd5-empty group. The work described here demonstrates that mucosal rAd5 can be used in a therapeutic capacity to elicit antigen-specific cellular immunity and further identifies a clinical candidate with immense potential for the treatment and prevention of human cervical cancer.

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Braun, M. R., Lindbloom, J. D., Moore, A. C., Hodgson, K. A., Dora, E. G., Tucker, S. N.. 2024-03-14. Elimination of human papillomavirus 16-induced tumors by a mucosal rAd5 therapeutic vaccination in a pre-clinical study. https://doi.org/10.1101/2024.03.11.584519

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