Guo Li-Li, Wang Gang-Cheng, Li Peng-Jie, Wang Cui-Mei, Liu Lin-Bo
Department of Plastic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Exp Ther Med. 2018 Jun;15(6):5394-5402. doi: 10.3892/etm.2018.6085. Epub 2018 Apr 23.
Viral vectors represent a potential strategy for the treatment of human malignant tumors. Currently, recombinant adenovirus vectors are commonly used as gene therapy vehicles, as it possesses a proven safety profile in normal human cells. The recombinant adenovirus system has an ability to highly express exogenous genes and increase the stability of the carrier, which is only transiently expressed in the host cell genome, without integrating. Malignant melanoma cells are produced by the skin, and melanocyte tumors that exhibit higher malignant degrees lead to earlier transfer and higher mortality. In the present study, a recombinant adenovirus (rAd) was generated to express Anti-programmed death-1 (rAd-Anti-PD-1) and used to investigate the efficacy in melanoma cells and tumors. The results demonstrated that B16-F10 cell growth was significantly inhibited and the apoptosis incidence rate was markedly promoted following rAd-PD-1 treatment. The present study demonstrated that the production of α and β interferon was increased, which led to the induction of dendritic cell (DCs) maturation in rAd-anti-PD-1-treated mice. The present study indicated that rAd-anti-PD-1 exhibited the ability to generate more cluster of differentiation (CD)4CD8 T cells and induce a PD-1-specific cytotoxic T lymphocyte through DC-targeted surface antigens in mice. This resulted in a further enhanced recognition of melanoma cells due to DCs being targeted by the rAd-anti-PD-1-encoded PD-1. Notably, mice treated with the rAd-anti-PD-1-targeted PD-1 demonstrated an improved protection compared with tumor-bearing mice from the challenge group treated with a recombinant gutless adenovirus and Anti-PD-1. In conclusion, the present study demonstrated that targeting the melanoma surface antigens via the rAd-anti-PD-1-infected tumor cells enhanced the ability of recombinant adenovirus to induce a potent tumor-inhibitory effect and antigen-specific immune response.
病毒载体是治疗人类恶性肿瘤的一种潜在策略。目前，重组腺病毒载体通常用作基因治疗载体，因为它在正常人类细胞中具有已证实的安全特性。重组腺病毒系统具有高表达外源基因和提高载体稳定性的能力，其在宿主细胞基因组中仅短暂表达，不进行整合。恶性黑色素瘤细胞由皮肤产生，恶性程度较高的黑色素细胞瘤会导致更早的转移和更高的死亡率。在本研究中，构建了一种表达抗程序性死亡蛋白1的重组腺病毒（rAd-Anti-PD-1），并用于研究其对黑色素瘤细胞和肿瘤的疗效。结果表明，rAd-PD-1处理后，B16-F10细胞生长受到显著抑制，凋亡发生率明显提高。本研究表明，rAd-anti-PD-1处理的小鼠中α和β干扰素的产生增加，导致树突状细胞（DCs）成熟。本研究表明，rAd-anti-PD-1能够在小鼠中通过DC靶向表面抗原产生更多的分化簇（CD）4CD8 T细胞，并诱导PD-1特异性细胞毒性T淋巴细胞。由于DCs被rAd-anti-PD-1编码的PD-1靶向，这导致对黑色素瘤细胞的识别进一步增强。值得注意的是，与用重组无肠腺病毒和抗PD-1处理的攻击组荷瘤小鼠相比，用rAd-anti-PD-1靶向PD-1处理的小鼠表现出更好的保护作用。总之，本研究表明，通过rAd-anti-PD-1感染的肿瘤细胞靶向黑色素瘤表面抗原可增强重组腺病毒诱导有效肿瘤抑制作用和抗原特异性免疫反应的能力。
