An Oncolytic Adenovirus Encoding SA-4-1BBL Adjuvant Fused to HPV-16 E7 Antigen Produces a Specific Antitumor Effect in a Cancer Mouse Model.
An Oncolytic Adenovirus Encoding SA-4-1BBL Adjuvant Fused to HPV-16 E7 Antigen Produces a Specific Antitumor Effect in a Cancer Mouse Model.
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DOI：
10.3390/vaccines9020149
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发表时间：
2021-02-12
期刊：
影响因子：
7.8
通讯作者：
Montes-de-Oca-Luna R
中科院分区：
文献类型：
--
作者：
Martinez-Perez AG;Perez-Trujillo JJ;Garza-Morales R;Ramirez-Avila NE;Loera-Arias MJ;Gomez-Gutierrez JG;Saucedo-Cardenas O;Garcia-Garcia A;Rodriguez-Rocha H;Montes-de-Oca-Luna R
人类乳头瘤病毒(HPV)占全球癌症病例的25%左右。HPV-16E7抗原是一种肿瘤相关抗原(TAA)，在HPV诱导的肿瘤中普遍表达，但其免疫原性低。4-1BBL与其受体的相互作用对天然免疫、获得性免疫和调节性免疫具有多效性，如果与DNA疫苗中的TAA融合，可以提高抗肿瘤效果，但其转染率和抗肿瘤效率较低。溶瘤病毒疗法可以选择性地在肿瘤细胞中复制，诱导细胞溶解，而且肿瘤细胞碎片可以被免疫细胞摄取，从而增强抗肿瘤反应，因此有望用于抗肿瘤基因治疗。在本研究中，我们在溶瘤腺病毒(OAD)系统中表达了与E7融合的免疫调节分子SA-4-1BBL。SA/E7/4-1BBLOAD体外感染TC-1肿瘤细胞和NIH-3T3非肿瘤细胞表明，只有肿瘤细胞被选择性破坏。此外，当加入信号肽(SP)时，两种细胞系的蛋白质表达都定位于内质网。最后，在HPV诱导的小鼠癌症模型中，可以检测到OAD的治疗溶瘤活性，当与E7和SP融合时，这一点可以得到改善。
Human papillomaviruses (HPVs) are responsible for about 25% of cancer cases worldwide. HPV-16 E7 antigen is a tumor-associated antigen (TAA) commonly expressed in HPV-induced tumors; however, it has low immunogenicity. The interaction of 4-1BBL with its receptor induces pleiotropic effects on innate, adaptive, and regulatory immunity and, if fused to TAAs in DNA vaccines, can improve the antitumor response; however, there is low transfection and antitumor efficiency. Oncolytic virotherapy is promising for antitumor gene therapy as it can be selectively replicated in tumor cells, inducing cell lysis, and furthermore, tumor cell debris can be taken in by immune cells to potentiate antitumor responses. In this study, we expressed the immunomodulatory molecule SA-4-1BBL fused to E7 on an oncolytic adenovirus (OAd) system. In vitro infection of TC-1 tumor cells and NIH-3T3 non-tumor cells with SA/E7/4-1BBL OAd demonstrated that only tumor cells are selectively destroyed. Moreover, protein expression is targeted to the endoplasmic reticulum in both cell lines when a signal peptide (SP) is added. Finally, in an HPV-induced cancer murine model, the therapeutic oncolytic activity of OAd can be detected, and this can be improved when fused to E7 and SP.
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DOI：
10.2147/cpaa.s46199
发表时间：
2013-09-02
期刊：
Clinical pharmacology : advances and applications
影响因子：
--
作者：
Li SY;Liu Y
通讯作者：
Liu Y
影响因子：
14.8
作者：
Luo, Jinyong;Deng, Zhong-Liang;He, Tong-Chuan
通讯作者：
He, Tong-Chuan
影响因子：
2.9
作者：
Perez-Trujillo JJ;Garza-Morales R;Barron-Cantu JA;Figueroa-Parra G;Garcia-Garcia A;Rodriguez-Rocha H;Garcia-Juarez J;Muñoz-Maldonado GE;Saucedo-Cardenas O;Montes-De-Oca-Luna R;Loera-Arias MJ
通讯作者：
Loera-Arias MJ
影响因子：
4.7
作者：
Howells A;Marelli G;Lemoine NR;Wang Y
通讯作者：
Wang Y
影响因子：
9
作者：
Ma, Jing;Ramachandran, Mohanraj;Essand, Magnus
通讯作者：
Essand, Magnus