Development of DNA vaccine against tumors expressing CEA using scFv (Single Chain Fragment Variable) derived of the idiotypic antibody 6.C4

• Grant number: 12/21861-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2013
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Sang Won Han
• Grantee: Sang Won Han
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Bryan Eric Strauss ; Jane Zveiter de Moraes

Abstract

The carcinoembryonic antigen (CEA) is a tumor marker for cancers of epithelial origin, which is expressed during embryonic life and is present in some normal adult tissues: consequently, CEA is recognized as a self-antigen by the immune system. The replacement of antigen for immunization by anti-idiotypic antibody has been considered a promising strategy to break tolerance in some types of tumor-associated antigens. Recently our group described the construction of two forms of single chain fragment variable (scFv) from the monoclonal anti-idiotypic 6.C4, giving rise to scFv-6.C4, which have the ability to mimic CEA. Balb/c mice immunized with plasmids expressing scFv-6.C4 produced antibodies able to recognize the CEA in vitro. It was a clear demonstration of proof-of-principle. This work was awarded by the International Union Against Cancer in 2002, and also generated some publications. Despite the success in creating scFv able to mimic CEA, there are several questions to be answered before it becomes a DNA vaccine capable of treating cancers that express CEA: 1) Immune responses against tumor-associated antigens are usually weak. Does the immune response generated by immunization with scFv-6.C4 is sufficient to retard / inhibit tumor growth? 2) How can we improve this weak immune response to DNA vaccination? Increasing the expression of the scFv-6.C4 antigen and / or administering an adjuvant together? 3) DNA vaccination with scFv-6.C4 may work for both preventive and therapeutic purpose? 4) The mice do not express CEA. How can we get an animal model with tumors expressing CEA to validate DNA vaccines? 5) What type of immune response is induced by vaccination with scFv 6.C4? These questions are the main objectives of this project. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZANETTI, BIANCA FERRARINI; FERREIRA, CAMILA PONTES; VASCONCELOS, JOSE RONNIE CARVALHO; HAN, SANG WON. Adjuvant properties of IFN-gamma and GM-CSF in the scFv6.C4 DNA vaccine against CEA-expressing tumors. Gene Therapy, JUN 2021. (12/21861-1, 13/17224-9)

ZANETTI, BIANCA FERRARINI; FERREIRA, CAMILA PONTES; VASCONCELOS, JOSE RONNIE CARVALHO; HAN, SANG WON. Adjuvant properties of IFN-gamma and GM-CSF in the scFv6.C4 DNA vaccine against CEA-expressing tumors. Gene Therapy, v. 30, n. 1-2, p. 10-pg., 2021-06-09. (13/17224-9, 12/21861-1)

DENAPOLI, PRISCILA M. A.; ZANETTI, BIANCA F.; DOS SANTOS, ADARA A.; DE MORAES, JANE Z.; HAN, SANG W.. Preventive DNA vaccination against CEA-expressing tumors with anti-idiotypic scFv6.C4 DNA in CEA-expressing transgenic mice. CANCER IMMUNOLOGY IMMUNOTHERAPY, v. 66, n. 3, p. 333-342, MAR 2017. (12/21861-1)

ZANETTI, BIANCA FERRARINI; FERREIRA, CAMILA PONTES; CARVALHO DE VASCONCELOS, JOSE RONNIE; HAN, SANG WON. scFv6.C4 DNA vaccine with fragment C of Tetanus toxin increases protective immunity against CEA-expressing tumor. Gene Therapy, v. 26, n. 10-11, p. 441-454, NOV 2019. (13/17224-9, 12/21861-1)

DE MELO, SUELY MAYMONE; BITTENCOURT, SIMONE; FERRAZOLI, ENEAS GALDINI; DA SILVA, CLIVANDIR SEVERINO; DA CUNHA, FLAVIA FRANCO; DA SILVA, FLAVIA HELENA; STILHANO, ROBERTA SESSA; ANDRADE DENAPOLI, PRISCILA MARTINS; ZANETTI, BIANCA FERRARINI; MATSUMOTO MARTIN, PRISCILA KEIKO; et al. The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor. PLoS One, v. 10, n. 6, JUN 12 2015. (12/21861-1)