The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing.
The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing.
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武装溶瘤腺病毒ZD55-IL-24除直接杀伤外，还通过将肿瘤细胞从自体状态转变为非自体状态来根除黑色素瘤
DOI：
10.1038/s41419-020-03223-0
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发表时间：
2020-11-30
影响因子：
9
通讯作者：
Liu XY
中科院分区：
文献类型：
--
作者：
Hu HJ;Liang X;Li HL;Du CM;Hao JL;Wang HY;Gu JF;Ni AM;Sun LY;Xiao J;Hu JQ;Yuan H;Dai YS;Jin XT;Zhang KJ;Liu XY
ZD 55-IL-24与溶瘤腺病毒ONYX-015相似但上级，但观察到的治疗效果的确切机制仍不清楚。在此，我们试图阐明ZD 55-IL-24在免疫活性和免疫受损小鼠模型中的潜在抗肿瘤机制。我们发现，ZD 55-IL-24根除在B16荷瘤免疫活性小鼠模型中建立的黑色素瘤不是通过经典的直接杀伤途径，而是主要通过诱导全身抗肿瘤免疫的间接途径。与目前流行的观点不一致，我们进一步的结果表明，ZD 55-IL-24可以在携带B16的免疫活性小鼠模型中诱导抗肿瘤免疫，实际上不是由于其裂解肿瘤细胞并释放必需元素的能力，例如肿瘤相关抗原（TAA），而是因为它能够在肿瘤细胞中贴上“非我”标签，然后将肿瘤细胞从“自我”状态转变为“非我”状态，而不会导致肿瘤细胞死亡。在携带B16的免疫活性小鼠模型中观察到的ZD 55-IL-24的抗黑色素瘤功效实际上仅由病毒载体引起。此外，我们还注意到，ZD 55-IL-24可以通过抑制血管生成来抑制荷B16免疫活性小鼠模型中的肿瘤生长，尽管其作用很小。与B16荷瘤小鼠模型相比，ZD 55-IL-24主要通过经典的直接杀伤途径消除A375荷瘤小鼠模型中已建立的黑色素瘤，而不是通过抗肿瘤免疫途径和抗血管生成途径。这些发现使我们对ZD 55-IL-24有了更全面、更深刻的认识，并为其今后的修饰和药物开发提供了更坚实的理论基础。
ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a “nonself” label in tumor cells and then turn the tumor cells from the “self” state into the “nonself” state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.
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影响因子：
12.8
作者：
Kumar P;Bhattacharya P;Prabhakar BS
通讯作者：
Prabhakar BS
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
3.7
作者：
Jiang H;Clise-Dwyer K;Ruisaard KE;Fan X;Tian W;Gumin J;Lamfers ML;Kleijn A;Lang FF;Yung WK;Vence LM;Gomez-Manzano C;Fueyo J
通讯作者：
Fueyo J
影响因子：
16.8
作者：
Ferrarini, M;Ferrero, E;Zocchi, MR
通讯作者：
Zocchi, MR
MDA-7/IL-24：IL-10基因家族的独特成员，促进了以癌为靶向的毒性。
影响因子：
13
作者：
Dash, Rupesh;Bhutia, Sujit K.;Azab, Belal;Su, Zhao-zhong;Quinn, Bridget A.;Kegelmen, Timothy P.;Das, Swadesh K.;Kim, Keetae;Lee, Seok-Geun;Park, Margaret A.;Yacoub, Adly;Rahmani, Mohammed;Emdad, Luni;Dmitriev, Igor P.;Wang, Xiang-Yang;Sarkar, Devanand;Grant, Steven;Dent, Paul;Curiel, David T.;Fisher, Paul B.
通讯作者：
Fisher, Paul B.