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cattle (38); and circulating antigen followed by antibody response to hepatitis 
B -surface antigen in mice (39). Our own group has demonstrated immune 
response to human carcinoembryonic antigen using intramuscular injection of 
plasmid DNA in mice (40). 
2.4 Immune response to CEA can occur in mice and non-human primates and 
confer both immunoprotection and therapy in syngeneic CEA expressing 
murine tumor models. 
Schlom’s group (41) described the cloning of the CEA gene from a human colon 
tumor cell library. The 2.4 Kb cDNA clone contained the complete coding 
sequence for CEA and was successfully inserted into a vaccinia virus genome 
(NYC attenuated strain). This group (42) inserted the cDNA clone for CEA into 
the murine colon carcinoma cell line, MC-38, and demonstrated that this tumor 
was now CEA positive with cell surface display of intact CEA (180 Kd). The 
recombinant virus vaccine (rV-CEA) induced high titers of IgG antibodies to 
CEA; delayed hypersensitivity skin test reactivity and lymphoblastic 
transformation to CEA; cytolytic T cell responses specific for CEA positive MC- 
38 tumor cells; immunoprotection against challenge with 2 x 10^ MC-38/CEA 
tumor cells; and anti-tumor effects when vaccine therapy began 7 days following 
challenge with 2 x 10^ MC-38/CEA cells (20). These effects were all CEA 
specific clearly showing that this molecule can function as an effective target for 
tumor immunity. There were no toxic effects in mice despite the presence of 
homologous CEA family members in normal rodent tissues (16). We have 
preliminary data to indicate that CEA polynucleotide vaccines can provide 
immunoprotection against the same MC-38/CEA tumor challenge (2 x 10^ cells). 
Schlom’s group also extimined the immunogenicity of the rV-CEA construct in 
primates (43). Adult rhesus monkeys received immunizations with the rV 
(NYC)-CEA and developed specific anti-CEA antibody responses, delayed 
hypersensitivity skin tests to CEA and lymphoblastic transformation to CEA. 
These animals have NCA (non-specific cross-reacting antigen) on their 
granulocyte surface. No toxicity or granulocytopenia was noted and no antibody 
to NCA was detected. 
Thus, the pre-clinical data demonstrate the defined molecular nature of this tumor- 
associated antigen with solid evidence of its immunogenicity in mice and non- 
human primates. No toxicity has been noted in these models in regard to cross- 
reactivity with other members of the CEA frunily residing in normal tissues. 
Based upon these pre-clinical observations, a phase I trial of recombinant 
vaccinia-CEA in patients with advanced colorectal adenocarcinoma is ongoing at 
the Clinical Research Center at NIH with immunologic monitoring conducted by 
the UAB Immunology Laboratory directed by Dr. Robert M. Conry of this 
protocol. Twenty patients have received single and multiple immunizations 
without toxicity. A phase Ib trial of recombinant vaccinia-CEA in patients with 
resected Dukes’ C adenocarcinoma of the colon (who have completed adjuvant 
5-FU/levamisole) is ongoing at the UAB Cancer Center. This trial will examine 
Recombinant DNA Research, Volume 19 
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