ENHANCED IMMUNE-RESPONSES AND ANTITUMOR-ACTIVITY BY BACULOVIRUS RECOMBINANT CARCINOEMBRYONIC ANTIGEN (CEA) IN MICE PRIMED WITH THE RECOMBINANT VACCINIA CEA

Carcinoembryonic antigen (CEA), a glycosylated protein of Mr 180, is one of the most widely studied oncofetal antigens. A majority of gastrointestinal cancers as well as breast and non-small-cell lung carcinomas express CEA. CEA thus represents a potential target for immunotherapy of several carcinoma types. A recombinant vaccinia-CEA virus (rV-CEA) was previously shown to induce anti-tumor activity in an experimental murine model after three rV-CEA inoculations. However, because the majority of cancer patients have received a previous smallpox vaccination, a long-lasting immune memory and/or induced anamnestic responses against vaccinia proteins may prevent repetitive boosting with the recombinant vaccinia virus expressing CEA. Therefore, other types of vaccines may be required to boost the anti-CEA immune response; one such schema would be the use of purified CEA as a boost in hosts given one administration of rV-CEA. Commercially available sources of CEA are usually derived from liver metastases extracts and are sometimes contaminated with nonspecific cross-reactive antigen. We have previously generated a recombinant source of full-length human CEA using a baculovirus expression system (bV-CEA). bV-CEA was shown to be glycosylated differently than native CEA, but it contains at least 10 epitopes found on native CEA (nCEA). Moreover, bV-CEA was able to induce a humoral response against CEA present on human colorectal cancer cell lines. We have investigated here the effectiveness of bV-CEA and nCEA to boost both humoral and T-cell responses after a primary vaccination with the recombinant CEA vaccinia vaccine. The results indicate that the combination immunization regimen based on priming with rV-CEA followed by a bV-CEA boost is superior in the induction of immune responses and anti-tumor activity than using bV-CEA alone or one inoculation of rV-CEA as vaccine. The studies reported here thus provide evidence for the use of bV-CEA as a boost following primary immunization with rV-CEA.