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一步法人工抗原提呈细胞疫苗诱导强烈的效应性 CD8 T 细胞应答。

One-step artificial antigen presenting cell-based vaccines induce potent effector CD8 T cell responses.

机构信息

Baylor Scott & White Research Institute, Baylor Institute for Immunology Research, Dallas, TX, USA.

出版信息

Sci Rep. 2019 Dec 12;9(1):18949. doi: 10.1038/s41598-019-55286-5.

Abstract

The production and wide use of artificial antigen presenting cells (aAPCs) in the clinic as cancer immunotherapeutics are hindered by the need of identifying immunogenic cancer antigens and production of recombinant patient-specific major histocompatibility complexes (MHC) loaded with these peptides. To overcome these limitations, in this study, we tested the idea of whether peptide-MHCs can directly be captured from cell lysates, including cancer cells using affinity beads, and used to initiate T cell responses. In theory, these affinity beads covered with the unknown peptide-MHC repertoire captured from the cancer cells could interact with a wide range of antigen-specific T cells and promote anti-cancer responses. Indeed, we found that we can successfully pull-down peptide-MHCs from cell lysates and the aAPCs generated using this technique were able to induce antigen-specific cytotoxic effector T cell responses that led to in vitro and in vivo tumor cell killing. In summary, we present here a novel technique to generate patient-specific aAPCs, that might have the potential to revolutionize the field of cancer vaccines, and provide patients with a vaccine in matters of days at minimal costs.

摘要

在临床上,作为癌症免疫疗法,人工抗原呈递细胞(aAPCs)的生产和广泛应用受到需要识别免疫原性癌症抗原和生产用这些肽负载的重组患者特异性主要组织相容性复合物(MHC)的限制。为了克服这些限制,在这项研究中,我们测试了这样一个想法,即肽-MHC 是否可以直接使用亲和珠从包括癌细胞在内的细胞裂解物中捕获,并且可以用于启动 T 细胞反应。从理论上讲,这些覆盖有从癌细胞中捕获的未知肽-MHC repertoire 的亲和珠可以与广泛的抗原特异性 T 细胞相互作用并促进抗癌反应。事实上,我们发现我们可以成功地从细胞裂解物中拉下肽-MHC,并且使用该技术产生的 aAPCs 能够诱导导致体外和体内肿瘤细胞杀伤的抗原特异性细胞毒性效应 T 细胞反应。总之,我们在这里提出了一种生成患者特异性 aAPCs 的新方法,该方法可能有潜力彻底改变癌症疫苗领域,并以最低的成本在几天内向患者提供疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62fd/6908577/4f5b2151182d/41598_2019_55286_Fig1_HTML.jpg

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