Recombinant Breast Cancer Vaccines
Abstract
ErbB-2 is a tumor associated antigen. Vaccination with wild-type ErbB-2 DNA induces effective anti-tumor immunity which includes a strong anti-ErbB-2 antibody response. To activate specific components of the immune response, DNA vaccines were constructed which direct recombinant ErbB-2 to the subcellular compartments of antigen processing and presentation. To induce ErbB-2 specific CTL, a recombinant cytoplasmic ErbB-2 which lacks kinase activity was constructed. CytE2 localizes in the cytoplasm and is rapidly degraded by the proteosome. Vaccination with cytE2 alone does not protect against an ErbB-2 expressing tumor. This may be due to a lack of CD4 T cell induction. To activate or replace ErbB-2 specific CD4 T cells, co-vaccination of cytE2A with cytokine genes was examined. Co-vaccination of cytE2A with either IL-2 or GM-CSF genes induced anti-ErbB-2 CTL and an effective anti-tumor immune response. To induce ErbB-2 specific CD4 T cells, a recombinant ErbB-2 which is targeted to the lysosome for MHC class II processing and presentation was constructed. Co-vaccination with E2-Lamp + GM-CSF induced effective anti-tumor immunity. This study demonstrates the feasibility of eliciting individual effector mechanisms by vaccination with targeted DNA constructs and protection against ErbB-2 expressing tumors without antibody activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA398196
Entities
People
- Shari A. Pilon
- Wei P. Shi
Organizations
- Wayne State University