title: Anti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins.
abstract: 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, they also 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.
authors: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors: Carlos R
authors: CR
authors: Figueiredo
authors: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors: Alisson L
authors: AL
authors: Matsuo
authors: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors: Mariana H
authors: MH
authors: Massaoka
authors: Microbiology and Virology Unit, Department of Biomedical, Biotechnological and Translational Sciences, Universitá degli Studi di Parma, Parma 43121, Italy.
authors: Luciano
authors: L
authors: Polonelli
authors: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil; Recepta Biopharma, São Paulo, SP, Brazil. Electronic address: luiztravassos@gmail.com.
authors: Luiz R
authors: LR
authors: Travassos
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000276:immunology; D056747:Immunomodulation; D061986:MCF-7 Cells; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D022801:Complementarity Determining Regions; D007136:Immunoglobulins; D010455:Peptides
keywords: Antitumor activity; CDR; Cytotoxicity; Melanoma; Peptide