The SNX-482 peptide from Hysterocrates gigas spider acts as an immunomodulatory molecule activating macrophages

Author(s)

Munhoz, Jaqueline ^[1] ; Thome, Rodolfo ^[2] ; Rostami, Abdolmohamad ^[2] ; Ishikawa, Larissa Lumi Watanabe ^[2] ; Verinaud, Liana ^[3] ; Raposo, Catarina ^{[1, 3]}

Affiliation

^[1] Univ Estadual Campinas UNICAMP, Fac Ciencias Farmaceut, BR-13083865 Campinas, SP - Brazil

^[2] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 - USA

^[3] Univ Estadual Campinas, Dept Biol Estrutural & Func, Inst Biol, Campinas - Brazil

• Document type: Journal article
• Source: Peptides; v. 146, DEC 2021.
• Web of Science Citations: 0

Abstract

Peptides are molecules that have emerged as crucial candidates for the development of anticancer drugs. Spider venoms are a rich source of peptides (venom peptides - VPs) with biological effects. VPs have been tested as adjuvants in the activation of cells of the immune system with the aim of improving immunotherapies for the treatment of neoplasms. In the present study, the effects of SNX-482, a peptide from the African tarantula Hysterocrates gigas, on macrophages were described. The results showed that the peptide activated M0 macrophages, increasing costimulatory molecules (CD40, CD68, CD80, CD83, CD86) involved in antigen presentation, and also augmenting the checkpoint molecules PD-L1, CTLA-4 and FAS-L; these effects were not concentration-dependent. SNX-482 also increased the release of IL-23 and upregulated the expression of ccr4, ifng, gzmb and pdcd1, genes important for the anticancer response. The pretreatment of macrophages with the peptide did not interfere in the modulation of T cells, and macrophages previously polarized to M1 and M2 profile did not respond to SNX-482. These findings represent the expansion of knowledge about the use of VPs in drug discovery, pointing to a potential new candidate for anticancer immunotherapy. Considering that most immunotherapies target the adaptive system, the modulation of macrophages (an innate immune cell) by SNX482 is especially relevant. (AU)

• 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: 19/03761-9 - Effects of P. nigriventer spider venom and its purified toxins in reprogramming M1 and M2 macrophages
• Grantee: Jaqueline de Lima Munhoz
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation