The development of
recombinant vaccines for specific
immunotherapy of
carcinoma represents a novel approach for the treatment of
breast cancer and other
tumor types. This article reviews the various parameters that should be considered in the development of
recombinant vaccines. Several
breast cancer associated
antigens are also discussed which may provide potential target molecules. The human
carcinoembryonic antigen (CEA), which is expressed on approximately 50% of breast
cancers, represents one such target for
immunotherapy. To enhance the immunogenicity of this
antigen, a recombinant CEA-
vaccinia vaccine, designated rV-CEA, was produced. To study the effects of this
vaccine in an animal model, a murine colon
carcinoma cell line was transduced with CEA and transplanted into immunocompetent mice for protection and
therapy studies. Pre-clinical toxicity studies were also conducted in non-human primates. The results of these studies showed the
rV-CEA vaccine to be immunogenic and safe in both rodents and primates, and to elicit good anti-
tumor responses in the rodent model. In a Phase I clinical trial in metastatic breast, lung, and
colorectal cancer patients involving three immunizations of rV-CEA, at three dose levels, enhancement of T-cell and antibody responses to vaccinia virus
proteins were observed with no toxicity. Specific T-cell responses were studied via stimulation of peripheral blood lymphocytes with specific
peptide epitopes from the CEA molecule. These studies demonstrated clear cut differences in establishment of T-cell lines pre- versus post-immunization. The T-cell lines were shown to be CD8+ and/or CD4+/CD8+, to lyse EBV transformed B-cells transduced with the CEA gene, and to lyse CEA positive
carcinoma cells in a HLA restricted manner. Thus, in a Phase I clinical trial the
rV-CEA vaccine has been shown to stimulate a CTL response specific for CEA defined
epitopes in
cancer patients.