Abstract B105: A cancer vaccine targeting many neoantigens is required for effective eradication of large tumors

A. D’Alise, G. Leoni, G. Cotugno, F. Troise, F. Langone, Imma Fichera, M. Lucia, Rosa Vitale, Adriano Leuzzi, Veronica Bignone, E. D. Matteo, Fabio Giovanni Tucci, L. Avalle, V. Poli, A. Lahm, M. Catanese, A. Folgori, S. Colloca, A. Nicosia, E. Scarselli
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Abstract

Cancer neoantigens (nAgs) have the potential to elicit strong and tumor-specific immune responses and are, therefore, of great interest for cancer immunotherapeutic strategies, including therapeutic vaccines. Here we developed a novel neoantigen cancer vaccine based on adenoviruses derived from non-human Great Apes (GAds). GAds vaccination was highly effective in prophylactic or early therapeutic treatment of mouse tumors, independently of the number of encoded nAgs. In presence of high tumor burden, GAd has no antitumor effect unless combined with anti-PD1 treatment. In this more stringent setting, effectiveness of vaccination required the targeting of many neoantigens. Analysis of gene expression profile of tumors from responder mice showed greater diversification of the T cell repertoire with increased number of clonotypes in combo treated animals compared to anti-PD-1. Data suggest that GAd vaccines encoding a large number of nAgs can synergize with checkpoint inhibitors therapy by increasing the breadth of nAgs-specific T cells. Citation Format: Anna Morena D9Alise, Guido Leoni, Gabriella Cotugno, Fulvia Troise, Francesca Langone, Imma Fichera, Maria De Lucia, Rosa Vitale, Adriano Leuzzi, Veronica Bignone, Elena Di Matteo, Fabio Giovanni Tucci, Lidia Avalle, Valeria Poli, Armin Lahm, Maria Teresa Catanese, Antonella Folgori, Stefano Colloca, Alfredo Nicosia, Elisa Scarselli. A cancer vaccine targeting many neoantigens is required for effective eradication of large tumors [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B105.
摘要B105:为了有效根除大肿瘤,需要一种靶向多种新抗原的癌症疫苗
癌症新抗原(nag)有可能引发强烈的肿瘤特异性免疫反应,因此,对癌症免疫治疗策略(包括治疗性疫苗)有很大的兴趣。本研究以非人类类人猿(GAds)腺病毒为基础,研制了一种新型新抗原癌疫苗。GAds接种在小鼠肿瘤的预防或早期治疗中非常有效,与编码的nAgs数量无关。由于存在较高的肿瘤负荷,GAd除非联合抗pd1治疗,否则没有抗肿瘤作用。在这种更严格的情况下,疫苗接种的有效性需要针对许多新抗原。对反应小鼠肿瘤基因表达谱的分析显示,与抗pd -1相比,联合治疗动物的T细胞库更多样化,克隆型数量增加。数据表明编码大量nag的GAd疫苗可以通过增加nag特异性T细胞的宽度来与检查点抑制剂治疗协同作用。引文格式:Anna Morena D9Alise、Guido Leoni、Gabriella Cotugno、Fulvia Troise、Francesca Langone、Imma Fichera、Maria De Lucia、Rosa Vitale、Adriano Leuzzi、Veronica Bignone、Elena Di Matteo、Fabio Giovanni Tucci、Lidia Avalle、Valeria Poli、Armin Lahm、Maria Teresa Catanese、Antonella Folgori、Stefano Colloca、Alfredo Nicosia、Elisa Scarselli。为了有效根除大肿瘤,需要针对多种新抗原的癌症疫苗[摘要]。第四届CRI-CIMT-EATI-AACR国际癌症免疫治疗会议:将科学转化为生存;2018年9月30日至10月3日;纽约,纽约。费城(PA): AACR;癌症免疫学杂志,2019;7(2增刊):摘要nr B105。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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