Enhanced immune responses and anti-tumor 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Bei
R
R
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kantor
J
J
Kashmiri
S V
SV
Abrams
S
S
Schlom
J
J
D000818:Animals; D000970:Antineoplastic Agents; D001402:B-Lymphocytes / Q000276:immunology; D016367:Baculoviridae / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D016233:Immunotherapy, Active; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use*; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines