Immunotherapeutic Potential of Mollusk Hemocyanins in Murine Model of Melanoma
Emiliya Stoyanova,
Nikolina Mihaylova,
Nikola Ralchev,
Silviya Bradyanova,
Iliyan Manoylov,
Yuliana Raynova,
Krassimira Idakieva,
Andrey Tchorbanov
Affiliations
Emiliya Stoyanova
Department of Immunology, Stefan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 26, 1113 Sofia, Bulgaria
Nikolina Mihaylova
Department of Immunology, Stefan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 26, 1113 Sofia, Bulgaria
Nikola Ralchev
Department of Immunology, Stefan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 26, 1113 Sofia, Bulgaria
Silviya Bradyanova
Department of Immunology, Stefan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 26, 1113 Sofia, Bulgaria
Iliyan Manoylov
Department of Immunology, Stefan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 26, 1113 Sofia, Bulgaria
Yuliana Raynova
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Krassimira Idakieva
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Andrey Tchorbanov
Department of Immunology, Stefan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 26, 1113 Sofia, Bulgaria
The development of antitumor drugs and therapy requires new approaches and molecules, and products of natural origin provide intriguing alternatives for antitumor research. Gastropodan hemocyanins-multimeric copper-containing glycoproteins have been used in therapeutic vaccines and antitumor agents in many cancer models. Materials and Methods: We established a murine model of melanoma by challenging C57BL/6 mice with a B16F10 cell line for solid tumor formation in experimental animals. The anticancer properties of hemocyanins isolated from the marine snail Rapana thomasiana (RtH) and the terrestrial snail Helix aspersa (HaH) were evaluated in this melanoma model using various schemes of therapy. Flow cytometry, ELISA, proliferation, and cytotoxicity assays, as well as histology investigations, were also performed. Results: Beneficial effects on tumor growth, tumor incidence, and survival of tumor-bearing C57BL/6 mice after administration of the RtH or HaH were observed. The generation of high titers of melanoma-specific IgM antibodies, pro-inflammatory cytokines, and tumor-specific CTLs, and high levels of tumor-infiltrated M1 macrophages enhanced the immune reaction and tumor suppression. Discussion: Both RtH and HaH exhibited promising properties for applications as antitumor therapeutic agents and future experiments with humans.