B045:无抗原肿瘤疫苗治疗低免疫原性肿瘤

Miguel C. Sobral, Hua Wang, Alexander J. Najibi, Aileen W. Li, Catia Verbeke, D. Mooney
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摘要

某些化疗药物可引起肿瘤细胞的免疫原性死亡,增强抗肿瘤免疫应答。在这里,我们探索免疫原性化疗是否可以用于开发无抗原的癌症疫苗,通过将其与肿瘤周围注射的生物材料支架相结合,募集树突状细胞(dc)用于随后的抗原呈递和t细胞启动。发现含有粒细胞-巨噬细胞集落刺激因子(GM-CSF)和阿霉素- irgd偶联物的成孔海藻酸盐凝胶在体内可有效诱导4T1三阴性乳腺癌细胞凋亡,同时招募大量DCs。凝胶中CpG寡脱氧核苷酸的共包被显著增强了4T1细胞的免疫原性死亡,增加了全身肿瘤特异性CD8+ t细胞和CD8+ t细胞的肿瘤浸润,使肿瘤相关巨噬细胞向炎性m1样表型重极化,从而显著提高了抗肿瘤疗效。这种原位无抗原凝胶疫苗有望治疗免疫原性差的肿瘤,更广泛地说,可以作为一个简单的平台,实现原位个性化癌症疫苗接种,而无需识别肿瘤特异性抗原和制造个性化疫苗。引用格式:Miguel C. Sobral,王华,Alexander J. Najibi, Aileen Li, Catia S. Verbeke, David J. Mooney。无抗原肿瘤疫苗治疗低免疫原性肿瘤[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 B045。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Abstract B045: Antigen-free cancer vaccine to treat poorly immunogenic tumors
Certain chemotherapeutic drugs can elicit immunogenic death of tumor cells and enhance antitumor immune responses. Here we explore whether immunogenic chemotherapy can be utilized for the development of antigen-free cancer vaccines, by combining it with peritumorally injected biomaterial scaffolds that recruit dendritic cells (DCs) for subsequent antigen presentation and T-cell priming. Pore-forming alginate gels containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and a doxorubicin-iRGD conjugate were found to efficiently induce the apoptosis of 4T1 triple-negative breast cancer cells in vivo, while recruiting large numbers of DCs. The co-encapsulation of CpG oligodeoxynucleotides in the gel significantly enhanced the immunogenic death of 4T1 cells, increased systemic tumor-specific CD8+ T-cells and tumoral infiltration of CD8+ T-cells, repolarized tumor-associated macrophages towards an inflammatory M1-like phenotype, and resulted in significantly improved antitumor efficacy. This in situ antigen-free gel vaccine shows promise for the treatment of poorly immunogenic tumors, and more broadly, may serve as a facile platform to enable in situ personalized cancer vaccination without requiring identification of tumor-specific antigens and manufacturing of personalized vaccines. Citation Format: Miguel C. Sobral, Hua Wang, Alexander J. Najibi, Aileen Li, Catia S. Verbeke, David J. Mooney. Antigen-free cancer vaccine to treat poorly immunogenic 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 B045.
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