Vaccines to Breast Cancer Based on p53 Mutants.

Abstract

Abstract : The aim of this study was to test vaccines expressing mouse mutant or wild-type p53 for induction of protective immunity against challenge with tumor cell lines expressing either mutant or high levels of wild-type p53. Our goal is to develop an efficacious vaccine with broad applicability for the treatment of human breast cancer patients. The completed studies show that vaccinia virus recombinants expressing full-length wild-type p53 provide up to 70% protection to one of the model tumor cell lines investigated. Vaccine efficacy can be improved by using mouse IL-12 as an adjuvant This combination treatment also results in complete tumor regression in approximately 40% of mice carrying already established tumors. Tumor rejection (with or without IL- 12) is mediated by CD4+ and CB8+ T cells as well as by NK cells. The vaccine was less efficacious against some other tumor cell lines that expressed mutant p53 or high levels of mutant wild-type p53. DNA vaccines expressing varied forms of wild-type or mutant p53 were also shown to inhibit the growth of some but not all tumors overexpressed p53. The efficacy of the DNA vaccines was improved by expressing the protein as a fusion construct with an adenoviral leader sequence.