Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV+ Men.

Autor:	Gosens KCM; Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Amsterdam, the Netherlands.; Amsterdam UMC, University of Amsterdam, Department of Dermatology, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam, the Netherlands., van der Burg SH; Leiden University Medical Center, Department of Medical Oncology, Oncode Institute, Leiden, the Netherlands., Welters MJP; Leiden University Medical Center, Department of Medical Oncology, Oncode Institute, Leiden, the Netherlands., Boekestijn S; Leiden University Medical Center, Department of Medical Oncology, Oncode Institute, Leiden, the Netherlands., Loof NM; Leiden University Medical Center, Department of Medical Oncology, Oncode Institute, Leiden, the Netherlands., Quint WGV; DDL Diagnostic Laboratory, Rijswijk, the Netherlands., van Noesel CJM; Amsterdam UMC, University of Amsterdam, Department of Pathology, Amsterdam, the Netherlands., van der Wal AC; Amsterdam UMC, University of Amsterdam, Department of Pathology, Amsterdam, the Netherlands., Richel O; Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Amsterdam, the Netherlands.; Radboud University Medical Center, Department of Internal Medicine, Nijmegen, the Netherlands., Krebber WJTA; ISA Pharmaceuticals, Oegstgeest, the Netherlands., Melief CJM; ISA Pharmaceuticals, Oegstgeest, the Netherlands., de Vries HJC; Amsterdam UMC, University of Amsterdam, Department of Dermatology, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam, the Netherlands.; STI outpatient clinic, Department of Infectious Diseases, Public Health Service of Amsterdam (GGD Amsterdam), Amsterdam, the Netherlands., Prins JM; Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Oct 13; Vol. 29 (20), pp. 4109-4117.
DOI:	10.1158/1078-0432.CCR-22-3361
Abstrakt:	Purpose: Anal cancer is increasing in HIV+ men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I to II dose-finding study, we assessed the safety and efficacy of the human papillomavirus type 16 (HPV16) synthetic long peptide vaccine (SLP-HPV-01) in HIV+ MSM with HPV16-positive HGAIN. Patients and Methods: Four dosage schedules (1-5-10; 5-10-20; 10-20-40; and 40-40-40-40 μg) of SLP-HPV-01 were administered intradermally with a 3-week interval in 10 patients per dose level (DL). In each dose group, 5 patients also received 1 μg/kg pegylated IFNα-2b subcutaneously. Primary endpoints were safety and regression of HGAIN at 3, 6, and 12 months. Results: Eighty-one of 134 screened patients (60%) had HPV16-negative HGAIN lesions, leaving 53 eligible patients. Thirteen patients were excluded, leaving 40 men. The vaccine was well tolerated. One patient developed a generalized rash. The highest dosage level induced the strongest immune responses. There was no indication for stronger reactivity in the IFNα groups. Up to 18 months of follow-up, 8/38 intention-to-treat patients had a complete clinical and histologic response and one had a partial response (in total 9/38, 23.7%). At the highest dosage level, the clinical response was 4/10 (40%). Stronger immune responses were detected among clinical responders. Conclusions: The highest DL is safe, immunogenic, and associated with clinical responses to HPV16-induced lesions. However, as the majority of HGAIN is caused by the other HPV types, further studies should aim at pan-HPV vaccination to prevent or treat HGAIN. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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