title: Polynucleotide immunization of nonhuman primates against carcinoembryonic antigen.
abstract: In preparation for a Phase I trial of DNA immunization against carcinoembryonic antigen (CEA) in patients with colorectal carcinoma, we have produced a single plasmid DNA encoding CEA and hepatitis B surface antigen (HBsAg) under transcriptional regulatory control of two separate cytomegalovirus promoters within separate eukaryotic expression cassettes, designated pCEA/HBsAg. Hepatitis B surface antigen was included to provide an internal positive control for the efficacy of this immunization strategy without regard to the issue of breaking tolerance to a self-antigen. In the present work, we sought to examine the immunogenicity of this plasmid in a nonhuman primate model with close phylogenetic relationship to humans. Groups of pig-tailed macaques were immunized with pCEA/ HBsAg by i.m. injection or particle bombardment of the skin according to a dose and schedule thought to be optimal for the respective technique of DNA immunization. Both administration techniques produced humoral and lympho-proliferative responses of comparable magnitude. However, delayed type hypersensitivity to CEA and CEA-specific interleukin-2 release were observed only in the i.m. group, suggesting a qualitative difference in the character of the immune response elicited by the two techniques of DNA immunization. The antibody responses to CEA and HBsAg were surprisingly persistent in that all immunized animals maintained moderate antibody titers against both antigens for more than 15 months after the last boost. No toxicity was observed during 2 years of follow-up, including no measurable levels of anti-DNA antibody. This antitumor immunization strategy is presently being examined in patients with metastatic colorectal carcinoma using pCEA/HBsAg administered by i.m. injection.
authors.affiliation: The Gene Therapy Program, University of Alabama at Birmingham, Comprehensive Cancer Center, 35294, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Conry
authors.forename: S A
authors.initials: SA
authors.lastname: White
authors.forename: P N
authors.initials: PN
authors.lastname: Fultz
authors.forename: M B
authors.initials: MB
authors.lastname: Khazaeli
authors.forename: T V
authors.initials: TV
authors.lastname: Strong
authors.forename: K O
authors.initials: KO
authors.lastname: Allen
authors.forename: D L
authors.initials: DL
authors.lastname: Barlow
authors.forename: S E
authors.initials: SE
authors.lastname: Moore
authors.forename: P N
authors.initials: PN
authors.lastname: Coan
authors.forename: I
authors.initials: I
authors.lastname: Davis
authors.forename: D T
authors.initials: DT
authors.lastname: Curiel
authors.forename: A F
authors.initials: AF
authors.lastname: LoBuglio
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008254:Macaca nemestrina; D011119:Polynucleotides / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D006514:Hepatitis B Surface Antigens; D007376:Interleukin-2; D011119:Polynucleotides; D019444:Vaccines, DNA