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

从蜘蛛毒液中分离出的肽在体外调节树突状细胞:一种可能应用于胶质母细胞瘤肿瘤免疫疗法的策略

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作者:Felipe Cezar de Mato ,Natália Barreto ,Gabriel Cordeiro ,Jaqueline Munhoz ,Amanda Pires Bonfanti ,Thomaz A A da Rocha-E-Silva ,Rafael Sutti ,Priscilla B M Cruz ,Livia R Sanches ,André Luis Bombeiro ,Ghanbar Mahmoodi Chalbatani ,Liana Verinaud ,Catarina Rapôso

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-1β, TNF-α), 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.

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