Anti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins

Autor(es)

Figueiredo, Carlos R. ^[1] ; Matsuo, Alisson L. ^[1] ; Massaoka, Mariana H. ^[1] ; Polonelli, Luciano ^[2] ; Travassos, Luiz R. ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit UNONEX, Sao Paulo, SP - Brazil

^[2] Univ Parma, Dept Biomed Biotechnol & Translat Sci, Microbiol & Virol Unit, I-43121 Parma - Italy

^[3] Recepta Biopharma, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Peptides; v. 59, p. 14-19, SEP 2014.
• Citações Web of Science: 17

Resumo

Short synthetic peptides corresponding to sequences of complementarity-determining regions (CDRs) from different immunoglobulin families have been shown to induce antimicrobial, antiviral and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). Presently, we studied the in vitro and in vivo antitumor activity of synthetic peptides derived from conserved CDR sequences of different immunoglobulins against human tumor cell lines and murine B16F10-Nex2 melanoma aiming at the discovery of candidate molecules for cancer therapy. Four light-and heavy-chain CDR peptide sequences from different antibodies (C36-L1, HA9-H2, 1-H2 and Mg16-H2) showed cytotoxic activity against murine melanoma and a panel of human tumor cell lineages in vitro. Importantly, theyalso exerted anti-metastatic activity using a syngeneic melanoma model in mice. Other peptides (D07-H3, MN20v1, MS2-H3) were also protective against metastatic melanoma, without showing significant cytotoxicity against tumor cells in vitro. In this case, we suggest that these peptides may act as immune adjuvants in vivo. As observed, peptides induced nitric oxide production in bone-marrow macrophages showing that innate immune cells can also be modulated by these CDR peptides. The present screening supports the search in immunoglobulins of rather frequent CDR sequences that are endowed with specific antitumor properties and may be candidates to be developed as anti-cancer drugs. (C) 2014 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 10/51423-0 - Peptídeos bioativos e peptidases: atividades biológicas e imunobiológicas em doenças infecciosas e no câncer
• Beneficiário: Luiz Rodolpho Raja Gabaglia Travassos
• Modalidade de apoio: Auxílio à Pesquisa - Temático