Recombinant Breast Cancer Vaccine
Abstract
Anti-tumor immunity induced by full-length human ERBB-2 DNA constructs was ranked as wild-type ERBB-2 (E2) > tyrosine kinase deficient ERBB-2 (E2A) > cytoplasmic E2 (cytE2) > cytE2A. Cytoplasmic E2 and its tyrosine kinase deficient counterpart cytE2A, both encode a protein targeted to and rapidly degraded in the cytosol by the proteasomes. Anti-ErbB-2 antibody was induced by immunization with transmembrane but not cytoplasmic, ERBB-2 DNA. Although an excellent vaccine against D2F2/E2, vaccination with E2 DNA was only moderately effective against D2F2/cytE2 tumor. Protection against both D2F2/E2 and D2F2/cytE2 was achieved by co-vaccination with cytE2 or cytE2A and GM-CSF or IL-2 DNA, indicating effective immunogenic peptide presentation from cytoplasmic ErbB-2 and a need for costimulation. ErbB-2 specific CTL were detected in mice immunized with cytE2A and GM-CSF after tumor rejection. Co-vaccination with E2A and cytE2A induced synergistic anti-tumor activity, supporting enhanced peptide presentation from cytoplasmic ErbB-2. Transmembrane ErbB-2 DNA vaccination elicited both humoral and cellular immune responses and protected mice from D2F2/E2. Cytoplasmic ERBB-2 and cytokine DNA vaccination induced anti-tumor cellular, but not humoral responses. 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, 2000
- Accession Number
- ADA392397
Entities
People
- Shari Pilon
- Wei-Zen Wei
Organizations
- Wayne State University