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肿瘤细胞裂解物作为癌症疫苗设计的免疫原性来源。

Tumor cell lysates as immunogenic sources for cancer vaccine design.

作者信息

González Fermín E, Gleisner Alejandra, Falcón-Beas Felipe, Osorio Fabiola, López Mercedes N, Salazar-Onfray Flavio

机构信息

a Millennium Institute on Immunology and Immunotherapy; Institute of Biomedical Sciences; Faculty of Medicine ; University of Chile ; Santiago , Chile.

出版信息

Hum Vaccin Immunother. 2014;10(11):3261-9. doi: 10.4161/21645515.2014.982996.

Abstract

Autologous dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) are a promising immunological tool for cancer therapy. These stimulate the antitumor response and immunological memory generation. Nevertheless, many patients remain refractory to DC approaches. Antigen (Ag) delivery to DCs is relevant to vaccine success, and antigen peptides, tumor-associated proteins, tumor cells, autologous tumor lysates, and tumor-derived mRNA have been tested as Ag sources. Recently, DCs loaded with allogeneic tumor cell lysates were used to induce a potent immunological response. This strategy provides a reproducible pool of almost all potential Ags suitable for patient use, independent of MHC haplotypes or autologous tumor tissue availability. However, optimizing autologous tumor cell lysate preparation is crucial to enhancing efficacy. This review considers the role of cancer cell-derived lysates as a relevant source of antigens and as an activating factor for ex vivo therapeutic DCs capable of responding to neoplastic cells. These promising therapies are associated with the prolonged survival of advanced cancer patients.

摘要

负载肿瘤相关抗原(TAA)的自体树突状细胞(DC)是一种很有前景的癌症免疫治疗工具。这些细胞可刺激抗肿瘤反应并产生免疫记忆。然而,许多患者对DC疗法仍不敏感。将抗原(Ag)递送至DC与疫苗的成功相关,抗原肽、肿瘤相关蛋白、肿瘤细胞、自体肿瘤裂解物和肿瘤衍生的mRNA都已作为Ag来源进行了测试。最近,负载同种异体肿瘤细胞裂解物的DC被用于诱导强烈的免疫反应。该策略提供了几乎所有适合患者使用的潜在Ag的可重复来源,而与MHC单倍型或自体肿瘤组织的可用性无关。然而,优化自体肿瘤细胞裂解物的制备对于提高疗效至关重要。本综述探讨了癌细胞衍生裂解物作为抗原相关来源以及作为能够对肿瘤细胞作出反应的离体治疗性DC的激活因子的作用。这些有前景的疗法与晚期癌症患者的生存期延长相关。

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