摘要
肿瘤衍生的自体抗原肽与分子量为70 kDa的内源性家庭热休克蛋白(HSP70)结合时能够诱导有效的抗肿瘤T细胞反应。然而,基于HSP的疫苗的疗效,从临床实用角度看仍有一定的局限性,包括对外来非热休克蛋白的免疫反应的激活。在这项研究中,我们重建体外复合物,该复合物由重组人HSPs70(重组人HSP70A1B和HSC70混合物,hrHSPs70)与来源于小鼠B16F10黑色素瘤细胞裂解液(PepMCL)的抗原低量肽组成,并研究这些复合物在黑色素瘤小鼠模型中激活抗肿瘤免疫的预防潜能。我们的研究结果表明,研制的预防性疫苗可诱发黑色素瘤特异性免疫应答和抗黑色素瘤作用。这些结果表明,hrHSPs70具有重组配合物和从体外肿瘤细胞溶解产物获得的肽的能力,因此,hrHSPs70可以被用来投递多聚抗原肽到抗原递呈细胞内(APC)激活效应细胞。以这种方式设计基于hrHSPs70的预防性疫苗诱导免疫反应,导致显著的抑制肿瘤的生长和转移的效应。
关键词: 抗肿瘤免疫,热休克蛋白70,肿瘤细胞裂解物,抗肿瘤疫苗。
Current Molecular Medicine
Title:Prophylactic Admission of an In Vitro Reconstructed Complexes of Human Recombinant Heat Shock Proteins and Melanoma Antigenic Peptides Activates Anti-Melanoma Responses in Mice
Volume: 15 Issue: 5
Author(s): L. V. Savvateeva, A. M. Schwartz, L. B. Gorshkova, N. V. Gorokhovets, V. A. Makarov, V. P. Reddy, G. Aliev and A. A. Zamyatnin
Affiliation:
关键词: 抗肿瘤免疫,热休克蛋白70,肿瘤细胞裂解物,抗肿瘤疫苗。
摘要: Tumor-derived autologous antigenic peptides when bound to endogenous 70 kDa family heat shock proteins (HSP70) are able to induce effective T-cell responses against tumors. However, efficacy of HSPbased vaccines in clinical practical stand point still has a number of certain limitations including an activation of immune responses against alien non-human HSPs. In this study we reconstructed the complexes of human recombinant HSPs70 (human recombinant HSP70A1B and HSC70 mixture; hrHSPs70) with antigenic lowweight peptides derived from mice B16F10 melanoma cell lysate (PepMCL) in vitro and investigated the prophylactic potential of these complexes to activate anti-tumor immunity in melanoma mouse model. Our results demonstrate that the developed prophylactic vaccine elicits melanoma-specific immune responses and anti-tumor effects against melanoma. These results suggest that hrHSPs70 has capability to reconstitute complexes with peptides obtained from tumor cells lysates in vitro and, therefore, can be used for delivery of multiple antigenic peptides into antigen-presenting cells (APCs) to activate effectors cells. Designed in such a way hrHSPs70-based prophylactic vaccines induce immune responses resulting in a significant efficient prevention of tumor growth and metastases.
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L. V. Savvateeva, A. M. Schwartz, L. B. Gorshkova, N. V. Gorokhovets, V. A. Makarov, V. P. Reddy, G. Aliev and A. A. Zamyatnin , Prophylactic Admission of an In Vitro Reconstructed Complexes of Human Recombinant Heat Shock Proteins and Melanoma Antigenic Peptides Activates Anti-Melanoma Responses in Mice, Current Molecular Medicine 2015; 15 (5) . https://dx.doi.org/10.2174/1566524015666150630125024
DOI https://dx.doi.org/10.2174/1566524015666150630125024 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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