DNA Vaccination to Overcome Peripheral Tolerance
Abstract
The vaccination efficacy of DNA encoding autologous rat ErbB-2 (neu) or heterologous human ErbB-2 (Her-2) is compared in rat neu transgenic mice (BALB neuT). Cross reactivity between Her-2 and rat neu was tested initially by immunizing normal mice twice, i.m. with pEFBosGM-CSF and pCMVE2TM orpCDneuTM. E2TM and neuTM encodes the extracellular (ECD) and transmembrane (TM) domains of Her-2 and neu, respectively. Immunized mice were challenged with mammary tumor D2F2 expressing Her-2 (D2F2/E2) or neu (D2F2/neu). All mice immunized with E2TM or neuTM rejected tumors expressing the corresponding antigen. There is significant cross-protection against tumors expressing the non-corresponding ErbB-2, although the antibodies demonstrated little cross-reactivity. When tested in neuT mice which are tolerant to rat neu, neuTM but not E2TM delayed spontaneous tumorigenesis. Therefore, Her-2 and rat neu are cross-reactive antigens in normal mice, but only autologous neu, not heterologous Her-2 induced protective immunity in NeuT transgenic mice. This may indicate a lack of cross-reactivity of antibodies which are critical in inhibiting NeuT tumor. To enhance the immunogenicity of autologous ErbB-2, an adjuvant sequence of Pan DR Reactive Epitope (PADRE) has been cloned into human ErbB-2 and the immunogenicity is being tested.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA423080
Entities
People
- Wei-Zen Wei
Organizations
- Wayne State University