Polynucleotide immunization of nonhuman primates against carcinoembryonic antigen.

Academic Article

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.
  • Published In

    Keywords

  • Animals, Antibodies, Antibody Formation, Cancer Vaccines, Carcinoembryonic Antigen, Female, Hepatitis B Surface Antigens, Immunity, Cellular, Immunization, Interleukin-2, Lymphocyte Activation, Macaca nemestrina, Polynucleotides, Vaccines, DNA
  • Author List

  • Conry RM; White SA; Fultz PN; Khazaeli MB; Strong TV; Allen KO; Barlow DL; Moore SE; Coan PN; Davis I
  • Start Page

  • 2903
  • End Page

  • 2912
  • Volume

  • 4
  • Issue

  • 11