Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.
Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.
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DOI：
10.1016/j.cell.2017.08.027
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发表时间：
2017-09-07
期刊：
影响因子：
64.5
通讯作者：
Long GV
中科院分区：
文献类型：
--
作者：
Ribas A;Dummer R;Puzanov I;VanderWalde A;Andtbacka RHI;Michielin O;Olszanski AJ;Malvehy J;Cebon J;Fernandez E;Kirkwood JM;Gajewski TF;Chen L;Gorski KS;Anderson AA;Diede SJ;Lassman ME;Gansert J;Hodi FS;Long GV
在这里，我们报告了一项1b期临床试验，测试了talimogene laherparepvec溶瘤病毒疗法对细胞毒性T细胞浸润和抗PD-1抗体pembrolizumab治疗效果的影响。21例晚期黑色素瘤患者接受拉他莫基治疗，随后接受派姆单抗联合治疗。治疗通常耐受良好，最常见的不良事件为疲劳、发热和寒战。未发生剂量限制性毒性。确认的客观缓解率为62%，根据免疫相关缓解标准，完全缓解率为33%。对联合治疗有反应的患者在拉他莫基治疗后肿瘤中的几种细胞亚群上的CD 8 + T细胞增加，PD-L1蛋白表达升高，以及IFN-γ基因表达升高。对联合治疗的应答似乎与基线CD 8 + T细胞浸润或基线IFN-γ特征无关。这些发现表明，溶瘤病毒疗法可能通过改变肿瘤微环境来提高抗PD-1治疗的疗效。与抗PD-1治疗相结合，肿瘤内注射一种溶瘤病毒，以增强对癌症的免疫识别，导致晚期黑色素瘤患者的高应答率。
Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8+ T cells, elevated PD-L1 protein expression, as well as IFN-γ gene expression on several cell subsets in tumors after talimogene laherparepvec treatment. Response to combination therapy did not appear to be associated with baseline CD8+ T cell infiltration or baseline IFN-γ signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. In combination with anti-PD-1 therapy, intratumoral injection of an oncolytic virus engineered to enhance immune recognition of cancer resulted in a high response rate in patients with advanced melanoma.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
黑色素瘤肿瘤微环境中PD-L1，IDO和T（REGS）的上调由CD8（+）T细胞驱动。
影响因子：
17.1
作者：
Spranger S;Spaapen RM;Zha Y;Williams J;Meng Y;Ha TT;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
45.3
作者：
Daud, Adil I.;Wolchok, Jedd D.;Hamid, Omid
通讯作者：
Hamid, Omid