Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer.
Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer.
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DOI：
10.1038/s41392-020-00448-5
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发表时间：
2021-01-20
影响因子：
39.3
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Ding Z;Li Q;Zhang R;Xie L;Shu Y;Gao S;Wang P;Su X;Qin Y;Wang Y;Fang J;Zhu Z;Xia X;Wei G;Wang H;Qian H;Guo X;Gao Z;Wang Y;Wei Y;Xu Q;Xu H;Yang L
新抗原因其高度的肿瘤特异性和免疫原性而被认为是肿瘤免疫治疗的最终靶点。树突状细胞（Dendritic cell，DCs）疫苗在治疗恶性肿瘤方面有着良好的应用前景。肺癌是世界上发病率和死亡率最高的致死性疾病。尽管近年来肺癌的靶向治疗和免疫检查点抑制剂发展迅速，但其疗效总体上仍不令人满意。因此，对于肺癌治疗存在迫切的未满足的临床需求。在这里，我们尝试使用个性化的新抗原肽脉冲自体DC疫苗治疗肺癌，并进行了一项由研究者发起的单臂、2个医疗中心的初步研究（ChiCTR-ONC-16009100，NCT 02956551）。入组的患者是接受过大量治疗的转移性肺癌患者。候选新抗原来源于新鲜活检组织的全外显子组测序和RNA测序以及生物信息学分析。本研究共入组12例患者。共进行了85次疫苗治疗，中位数为5剂/人（范围：3-14剂/人）。总共为每个患者选择12-30种基于肽的新抗原。所有治疗相关不良事件均为1-2级，且未因毒性作用而延迟给药。客观有效率为25%;疾病控制率为75%;中位无进展生存期为5.5个月，中位总生存期为7.9个月。本研究为新抗原疫苗治疗肺癌提供了新的证据，也为肺癌的治疗提供了新的机会。
Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3–14 doses/person). In total, 12–30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1–2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
9.7
作者：
Met, Ö;Wang, MJ;Claesson, MH
通讯作者：
Claesson, MH
癌症免疫疗法。树突状细胞疫苗增加了黑色素瘤新抗原特异性T细胞的广度和多样性。
DOI：
10.1126/science.aaa3828
发表时间：
2015-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carreno BM;Magrini V;Becker-Hapak M;Kaabinejadian S;Hundal J;Petti AA;Ly A;Lie WR;Hildebrand WH;Mardis ER;Linette GP
通讯作者：
Linette GP
影响因子：
12.3
作者：
Fisher S;Barry A;Abreu J;Minie B;Nolan J;Delorey TM;Young G;Fennell TJ;Allen A;Ambrogio L;Berlin AM;Blumenstiel B;Cibulskis K;Friedrich D;Johnson R;Juhn F;Reilly B;Shammas R;Stalker J;Sykes SM;Thompson J;Walsh J;Zimmer A;Zwirko Z;Gabriel S;Nicol R;Nusbaum C
通讯作者：
Nusbaum C