scFv6.C4 DNA vaccine with fragment C of Tetanus toxin increases protective immunity against CEA-expressing tumor

Author(s)

Zanetti, Bianca Ferrarini ^[1] ; Ferreira, Camila Pontes ^[2] ; Carvalho de Vasconcelos, Jose Ronnie ^{[2, 3]} ; Han, Sang Won ^{[1, 4]}

Affiliation

^[1] Univ Fed Sao Paulo, Res Ctr Gene Therapy, Escola Paulista Med, Rua Mirassol 207, BR-04044010 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Rua Botucatu 862, BR-04023062 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Inst Saude & Soc, Dept Biosci, Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Biophys, Escola Paulista Med, Rua Botucatu 862, BR-04023062 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Gene Therapy; v. 26, n. 10-11, p. 441-454, NOV 2019.
• Web of Science Citations: 0

Abstract

The carcinoembryonic antigen (CEA) is the main tumor-associated antigen of colorectal cancers. Previously, we developed a DNA vaccine using scFv6.C4, a CEA surrogate, against CEA-expressing tumors; 40% of the vaccinated mice were tumor-free after tumor challenge. In order to enhance vaccine efficacy, fragment C of Tetanus Toxin (FrC) was tested as adjuvant. C57BL/6J-CEA2682 mice were electroporated intramuscularly 4 times with uP-PS/scFv6.C4-FrC or uP-PS/scFv6.C4, challenged by s.c. injection of 1 x 10(5) MC38-CEA cells, and tumor growth was monitored over 100 days. The humoral and cellular immune responses were assessed by ELISA, immunocytochemistry, in-vitro lymphocyte proliferation, and CTL cytotoxicity assays. Immunization with uP-PS/scFv6.C4-FrC or uP-PS/scFv6.C4 induced similar anti-CEA antibody titers. However, immunocytochemistry analysis showed stronger staining with uP-PS/scFv6.C4-FrC-immunized mice sera. When challenged with MC38-CEA cells, 63% of the FrC-vaccinated mice did not develop tumors, half of the rest had a significant tumor growth delay, and the probability of being free of tumors was on average 40% higher than that of scFv6.C4-immunized mice. Addition of the adjuvant led to higher CD4+ and CD8+ proliferative responses and strong CD8+ CTL response against MC38-CEA cells. DNA immunization with scFv6.C4 and FrC increased antitumor effect via induction of high and specific humoral and cellular immune responses to CEA. (AU)

• FAPESP's process: 13/17224-9 - EFFECT OF CYTOKINES AND TETANUS TOXIN IN VACCINATION OF TUMORS EXPRESSING CEA WITH SCFV-6.C4
• Grantee: Bianca Ferrarini Zanetti
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/21861-1 - Development of DNA vaccine against tumors expressing CEA using scFv (Single Chain Fragment Variable) derived of the idiotypic antibody 6.C4
• Grantee: Sang Won Han
• Support Opportunities: Regular Research Grants