1. A carcinoembryonic antigen polynucleotide vaccine for human clinical use.
- Author
-
Conry RM, LoBuglio AF, Loechel F, Moore SE, Sumerel LA, Barlow DL, Pike J, and Curiel DT
- Subjects
- Adenocarcinoma immunology, Adenocarcinoma pathology, Animals, Antibodies, Neoplasm biosynthesis, Carcinoembryonic Antigen genetics, Colonic Neoplasms immunology, Colonic Neoplasms pathology, Cytomegalovirus genetics, DNA, Complementary administration & dosage, Enhancer Elements, Genetic, Female, Graft Rejection immunology, Humans, Injections, Intramuscular, Isoantibodies biosynthesis, Mice, Mice, Inbred C57BL, Neoplasm Metastasis, Neoplasm Transplantation immunology, Promoter Regions, Genetic, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins therapeutic use, Tumor Cells, Cultured, Vaccination, Adenocarcinoma prevention & control, Adenocarcinoma therapy, Antigens, Neoplasm immunology, Carcinoembryonic Antigen immunology, Colonic Neoplasms prevention & control, Colorectal Neoplasms therapy, DNA, Complementary genetics, Genes, Synthetic, Genetic Vectors, Recombinant Fusion Proteins immunology, Vaccines, Synthetic immunology
- Abstract
We have constructed a plasmid DNA encoding the full-length complementary DNA for human carcinoembryonic antigen (CEA) under transcriptional regulatory control of the cytomegalovirus early promoter/enhancer (pCEA) and demonstrated that this plasmid can function as a polynucleotide vaccine to elicit a CEA-specific immune response. This immune response protects against tumor challenge with syngeneic CEA-transduced colon carcinoma cells in mice. In the present work, the pCEA construct and purification method were modified to eliminate nonessential viral sequences, the ampicillin selectable marker, mutagens, and endotoxin to produce a reagent suitable for human clinical trials. The human use plasmid (pGT37) directs CEA expression at levels comparable with the original pCEA plasmid and can be propagated to yield large quantities of plasmid DNA based on kanamycin selection. A simple extraction technique greatly reduces contamination by endotoxin. Six weekly intramuscular injections of pGT37 elicited CEA-specific lymphoblastic transformation and antibody response in five of five mice and fully protected 10 of 10 mice against tumor challenge with syngeneic CEA-expressing colon cancer cells 42 days from the first plasmid injection. Thus, pGT37 encoding a tumor-associated antigen (CEA) has been shown to elicit cellular and humoral immune responses and mediate antitumor effects in vivo. This plasmid is suitable for human use and can be easily propagated in the laboratory.
- Published
- 1995