Adjuvant properties of IFN-gamma and GM-CSF in the scFv6.C4 DNA vaccine against CEA-expressing tumors

Author(s)

Zanetti, Bianca Ferrarini ; Ferreira, Camila Pontes ; Vasconcelos, Jose Ronnie Carvalho ; Han, Sang Won

• Document type: Journal article
• Source: Gene Therapy; v. 30, n. 1-2, p. 10-pg., 2021-06-09.

Abstract

Tumor-associated carcinoembryonic antigen (CEA) is a natural target for vaccines against colorectal cancers. Our previous experience with a DNA vaccine with scFv6.C4, a CEA surrogate, showed a CEA-specific immune response with 40% of tumor-free mice after challenge with B16F10-CEA and 47% with MC38-CEA cells. These percentages increased to 63% after using FrC as an adjuvant. To further enhance the vaccine efficacy, we tested GM-CSF and IFN gamma as adjuvants. C57BL/6J-CEA2682 mice were immunized 4 times with uP-PS/scFv6.C4, uP-PS/scFv6.C4 + uP-IFN gamma, or uP-PS/scFv6.C4 + uP-GMCSF. After one week, the mice were challenged with MC38-CEA, and tumor growth was monitored over 100 days. Immunization with scFv6.C4 and scFv6.C4 + GM-CSF resulted in a gradual increase in the anti-CEA antibody titer, while scFv6.C4 + IFN gamma immunization led to a rapid and sustained increase in the titer. The addition of IFN gamma also induced higher CD4 + and CD8 + responses. When challenged, almost 80% of the scFv6.C4 + IFN gamma-vaccinated mice did not develop tumors, while the others had a significant tumor growth delay. The probability of being tumor-free was 2700% higher using scFv6.C4 + IFN gamma than scFv6.C4. The addition of GM-CSF had no additional effect on tumor protection. DNA immunization with scFv6.C4 + IFN gamma, but not GM-CSF, increased the antitumor effect via readily sustained specific humoral and cytotoxic 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