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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A subtraction tolerization method of immunization allowed for Wilms' tumor protein-1 (WT1) identification in melanoma and discovery of an antitumor peptide sequence

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Massaoka, Mariana H. [1] ; Matsuo, Alisson L. [1] ; Figueiredo, Carlos R. [1] ; Girola, Natalia [1] ; Farias, Camyla F. [1] ; Pasqualoto, Kerly [2] ; Travassos, Luiz R. [1]
Total Authors: 7
[1] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit, Sao Paulo - Brazil
[2] Butantan Inst, Biochem & Biophys Lab, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF IMMUNOLOGICAL METHODS; v. 414, p. 11-19, DEC 1 2014.
Web of Science Citations: 2

On searching for melanoma transcription factors in a project focusing on internal antitumor peptide sequences from transcription factors, we found that a highly immunogenic component emerged upon using a subtraction tolerization method of immunization. While several conventional immunization procedures using whole melanoma cells induced a plethora of low affinity antibodies of various specificities, the subtraction tolerization method efficiently elicited mono-specific antibodies that recognized Wilms' tumor protein 1 (WT1), which is known as an important marker in melanoma prognosis and treatment For the tolerization step, pre-immunization of Balb/c mice with a membrane-rich preparation of glioblastoma U87 cells was used. The subsequent immunizations with SK-MEL-28 melanoma cells elicited antibodies strongly reacting with 50 and 55 kDa proteins, identified as WT1. Remarkably, this was the only component strongly reactive with these antibodies in a melanoma cell lysate. WT1 was then chosen as a target for selecting internally bioactive peptides. A hydrophilic Trojan peptide containing most of the zinc finger-2 domain of WT1 was synthesized and shown to inhibit SK-MEL-28 melanoma growth in vitro. The peptide WT1-pTj was also protective in vivo in a metastatic melanoma model and peptide-stimulated syngeneic dendritic cells reproduced the anti-melanoma effect of the unprotected peptide. Identification of antitumor peptides derived from major transcription factors represents a new tool to be explored in cancer research aiming at new therapeutic drugs. (C) 2014 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 10/51423-0 - Bioactive peptides and peptidases: biological and immunobiological activities in infectious diseases and cancer
Grantee:Luiz Rodolpho Raja Gabaglia Travassos
Support type: Research Projects - Thematic Grants