Recombinant Breast Cancer Vaccines
Abstract
Recombinant DNA vaccines encoding mutant ErbB-2, a transmembrane tyrosine kinase mediating oncogenic activity, have been constructed. In ERBB-2A (E2A), tyrosine kinase activity was eliminated by replacing the ATP binding residue 753 lysine with alanine. To generate cytosolic proteins, (cytE2, cytE2A), the ER signal sequence was deleted. Vaccination of BALB/c mice with DNA encoding transmembrane E2 or E2A induced anti-ErbB-2 antibodies and anti-tumor immunity, with E2 being more potent than E2A. Elimination of CD4 T cells prevented the induction of anti-ErbB-2 antibody which, therefore, serves as an indicator of CD4 help. Vaccination with cytE2A induced little protection against tumor growth and no antibody production. Co-vaccination with cytE2A and plasmid encoding IL-2 or GM-CSF protected 80% of mice against tumor challenge although no antibody was induced. These results indicated that CD4 T cell activation by transmembrane ERBB-2 but not cytoplasmic ERBB-2 was critical to anti-tumor immunity and can be replaced, in part, by cytokine co-vaccination and that signal transduction by ErbB-2 may contribute to ErbB-2 immunogenicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA384110
Entities
People
- Shari Pilon
Organizations
- Wayne State University