Preclinical study of a novel therapeutic vaccine for recurrent respiratory papillomatosis.

Preclinical study of a novel therapeutic vaccine for recurrent respiratory papillomatosis.
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DOI:
10.1038/s41541-021-00348-x
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发表时间:
2021-06-18
期刊:
影响因子:
9.2
通讯作者:
Allen CT
Allen CT
中科院分区:
医学1区
文献类型:
--
作者:
Lee MY;Metenou S;Brough DE;Sabzevari H;Bai K;Jochems C;Schlom J;Allen CT

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可能需要激活抗原特异性T淋巴细胞应答来治愈由低风险人乳头瘤病毒(lrHPV)慢性感染引起的疾病。需要安全有效的辅助疗法来治疗这些疾病。使用来自复发性呼吸道乳头状瘤病患者的T淋巴细胞的体外刺激、体内疫苗接种研究和携带表达lrHPV抗原的肿瘤的小鼠中的治疗研究,研究了表达设计用于引发针对HPV 6和HPV 11的免疫应答的蛋白质的新型大猩猩腺病毒疫苗PRGN-2012的安全性和有效性。PRGN-2012治疗诱导患者T淋巴细胞中的lrHPV抗原特异性应答。野生型小鼠的疫苗接种诱导E6特异性T淋巴细胞应答而无毒性。体内治疗性疫苗接种荷有已建立的表达HPV 6 E6的肿瘤的小鼠,导致HPV 6 E6特异性CD 8 + T淋巴细胞免疫的程度足以诱导肿瘤生长延迟。PRGN-2012在lrHPV慢性感染所致疾病患者中的临床研究是必要的。
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.
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影响因子: 4.6
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