Lee Maxwell Y, Metenou Simon, Brough Douglas E, Sabzevari Helen, Bai Ke, Jochems Caroline, Schlom Jeffrey, Allen Clint T
Section on Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, MD, USA.
Precigen, Inc., Germantown, MD, USA.
NPJ Vaccines. 2021 Jun 18;6(1):86. doi: 10.1038/s41541-021-00348-x.
Activation of antigen-specific T-lymphocyte responses may be needed to cure disorders caused by chronic infection with low-risk human papillomavirus (lrHPV). Safe and effective adjuvant therapies for such disorders are needed. The safety and efficacy of a novel gorilla adenovirus vaccine expressing a protein designed to elicit immune responses directed against HPV6 and HPV11, PRGN-2012, was studied using in vitro stimulation of T lymphocytes from patients with recurrent respiratory papillomatosis, in vivo vaccination studies, and therapeutic studies in mice bearing tumors expressing lrHPV antigen. PRGN-2012 treatment induces lrHPV antigen-specific responses in patient T lymphocytes. Vaccination of wild-type mice induces E6-specific T-lymphocyte responses without toxicity. In vivo therapeutic vaccination of mice bearing established HPV6 E6 expressing tumors results in HPV6 E6-specific CD8+ T-lymphocyte immunity of sufficient magnitude to induce tumor growth delay. The clinical study of PRGN-2012 in patients with disorders caused by chronic infection with lrHPV is warranted.
激活抗原特异性T淋巴细胞反应可能是治愈由低风险人乳头瘤病毒（lrHPV）慢性感染引起的疾病所必需的。对于此类疾病，需要安全有效的辅助治疗方法。我们使用来自复发性呼吸道乳头瘤病患者的T淋巴细胞进行体外刺激、体内疫苗接种研究以及对表达lrHPV抗原的肿瘤小鼠进行治疗研究，来研究一种新型大猩猩腺病毒疫苗PRGN - 2012的安全性和有效性，该疫苗表达一种旨在引发针对HPV6和HPV11免疫反应的蛋白质。PRGN - 2012治疗可在患者T淋巴细胞中诱导lrHPV抗原特异性反应。对野生型小鼠进行疫苗接种可诱导E6特异性T淋巴细胞反应且无毒性。对已建立表达HPV6 E6肿瘤的小鼠进行体内治疗性疫苗接种可产生足够强度的HPV6 E6特异性CD8 + T淋巴细胞免疫，从而诱导肿瘤生长延迟。有必要对PRGN - 2012在由lrHPV慢性感染引起疾病的患者中进行临床研究。
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