Title

Prophylactic Admission of an in Vitro Reconstructed Complexes of Human Recombinant Heat Shock Proteins and Melanom Antigenic Peptides Activates Anti-Melanoma Responses in Mice

Abstract

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 HSP-based 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 low-weight 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.

Department(s)

Chemistry

Keywords and Phrases

antigenic peptide; heat shock protein 70; peptides and proteins; unclassified drug; cancer vaccine; heat shock protein; heat shock protein 70; hybrid protein; melanoma antigen; peptide fragment; protein binding; animal cell; animal experiment; animal model; antigen presenting cell; antineoplastic activity; Article; controlled study; drug efficacy; effector cell; female; immune response; melanoma; mouse; nonhuman; prophylaxis; protein purification; tumor growth; tumor immunity; animal; chemistry; disease model; experimental melanoma; genetics; human; immunology; isolation and purification; melanoma; metabolism; mortality; pathology; tumor volume; Mus; Animals; Cancer Vaccines; Disease Models, Animal; Female; Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Melanoma; Melanoma, Experimental; Melanoma-Specific Antigens; Mice; Peptide Fragments; Protein Binding; Recombinant Fusion Proteins; Tumor Burden

International Standard Serial Number (ISSN)

15665240

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2015 Bentham Science Publishers B.V., All rights reserved.


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