Isolated Peptide from Spider Venom Modulates Dendritic Cells In Vitro: A Possible Application in Oncoimmunotherapy for Glioblastoma

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de Mato, Felipe Cezar ; Barreto, Natalia ; Cordeiro, Gabriel ; Munhoz, Jaqueline ; Bonfanti, Amanda Pires ; da Rocha-e-Silva, Thomaz A. A. ; Sutti, Rafael ; Cruz, Priscilla B. M. ; Sanches, Livia R. ; Bombeiro, Andre Luis ; Chalbatani, Ghanbar Mahmoodi ; Verinaud, Liana ; Raposo, Catarina

• Document type: Journal article
• Source: CELLS; v. 12, n. 7, p. 19-pg., 2023-04-01.

Abstract

Dendritic cells (DCs) vaccine is a potential tool for oncoimmunotherapy. However, it is known that this therapeutic strategy has failed in solid tumors, making the development of immunoadjuvants highly relevant. Recently, we demonstrated that Phoneutria nigriventer spider venom (PnV) components are cytotoxic to glioblastoma (GB) and activate macrophages for an antitumor profile. However, the effects of these molecules on the adaptive immune response have not yet been evaluated. This work aimed to test PnV and its purified fractions in DCs in vitro. For this purpose, bone marrow precursors were collected from male C57BL6 mice, differentiated into DCs and treated with venom or PnV-isolated fractions (F1-molecules < 3 kDa, F2-3 to 10 kDa and F3->10 kDa), with or without costimulation with human GB lysate. The results showed that mainly F1 was able to activate DCs, increasing the activation-dependent surface marker (CD86) and cytokine release (IL-1 beta, TNF-alpha), in addition to inducing a typical morphology of mature DCs. From the F1 purification, a molecule named LW9 was the most effective, and mass spectrometry showed it to be a peptide. The present findings suggest that this molecule could be an immunoadjuvant with possible application in DC vaccines for the treatment of GB. (AU)

• FAPESP's process: 15/04194-0 - Identification of new molecules with chemotherapeutic effect in human glioma and characterization of the mechanism
• Grantee: Catarina Raposo Dias Carneiro
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 22/03543-4 - Development of a new immunoadjuvant for the treatment of glioblastoma: molecule characterization and synthesis, preclinical and translational trials
• Grantee: Catarina Raposo Dias Carneiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/03051-9 - Identification of macrophages modulators molecules from spider venom: new perspectives for the treatment of cancer
• Grantee: Jaqueline de Lima Munhoz
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/23559-7 - Cell therapy with macrophages and NK cells modulated ex vivo by peptide isolated from animal venom: a new approach in immunotherapy for cancer
• Grantee: Amanda Pires Bonfanti
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/10003-3 - Molecular characterization of human gliomas and identification of neoplasms responsible for new biopharmaceuticals obtained from animal venom: a translational approach
• Grantee: Natália Barreto dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate