Linking Tumor Microenvironment State to HPV Therapeutic Vaccination Response in Respiratory Papillomatosis Patients!

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Recurrent Respiratory Papillomatosis (RRP) is a rare and debilitating neoplastic condition caused by chronic infection with human papillomavirus (HPV) types 6 or 11. It leads to the growth of papillomas in the upper aerodigestive tract. Currently, there are limited approved medical treatments available for RRP, necessitating repeated surgical procedures to maintain voice and airway function. PRGN-2012 is an immune-therapeutic utilizing a gorilla adenovirus, designed to enhance the immune response against HPV types 6 and 11.

This study represents the first human trial (phase 1) of PRGN-2012 as an adjuvant treatment for adult patients suffering from severe and aggressive RRP. The findings demonstrate that PRGN-2012 is overall safe and provides clinically meaningful benefits, with an impressive 50% complete response rate observed in patients receiving the highest dose. Responders exhibited a more robust expansion of peripheral HPV-specific T cells compared to nonresponders.

In-depth investigations also revealed important correlations. Patients who responded well to the treatment showed reduced baseline expression of papilloma-associated HPV genes, along with heightened interferon responses and increased expression of CXCL9 and CXCL10, which are key chemokines. Additionally, responders displayed greater infiltration of T cells into the papillomas. On the contrary, nonresponders exhibited higher levels of HPV and CXCL8 gene expression, increased presence of neutrophilic cells, and reduced T cell infiltration in the papillomas. These findings suggest that the expression of papilloma-associated HPV genes may influence interferon signaling and chemokine profiles within the tumor microenvironment, ultimately impacting the clinical response to therapeutic HPV vaccination in individuals with respiratory papillomatosis. This research highlights the potential for further development of PRGN-2012 as a promising treatment option for patients affected by RRP.

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