title: Safety and immunogenicity of a DNA vaccine encoding carcinoembryonic antigen and hepatitis B surface antigen in colorectal carcinoma patients.
abstract: Despite an abundance of preclinical data, relatively little is known regarding the efficacy of DNA vaccination in humans. Here, we present results from a dose-escalation clinical trial of a dual expression plasmid encoding carcinoembryonic antigen (CEA) and hepatitis B surface antigen (HBsAg) in 17 patients with metastatic colorectal carcinoma. CEA was selected as a prototypic tumor-associated self-antigen, and the HBsAg cDNA was included as a positive control for immune response to the DNA vaccine without relying upon breaking tolerance to a self-antigen. Groups of 3 patients received escalating single i.m. doses of the DNA vaccine at 0.1, 0.3, and 1.0 mg. Subsequent groups of 3 patients received three repetitive 0.3- or 1.0-mg doses at 3-week intervals. A final group of 2 patients received three repetitive 2.0 mg doses at 3-week intervals. Toxicity was limited to transient grade 1 injection site tenderness, fatigue, and creatine kinase elevations, each affecting a minority of patients in a non-dose-related manner. Repetitive dosing of the DNA vaccine induced HBsAg antibodies in 6 of 8 patients, with protective antibody levels achieved in four of these patients. CEA-specific antibody responses were not observed, but 4 of 17 patients developed lymphoproliferative responses to CEA after vaccination. No objective clinical responses to the DNA vaccine were observed among this population of patients with widely metastatic colorectal carcinoma. Nevertheless, this pilot trial has provided encouraging human immune response data in support of this vaccine technology.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama 35294-3300, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Conry
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Theresa V
authors.initials: TV
authors.lastname: Strong
authors.forename: Susan E
authors.initials: SE
authors.lastname: Moore
authors.forename: Karen O
authors.initials: KO
authors.lastname: Allen
authors.forename: Daunte L
authors.initials: DL
authors.lastname: Barlow
authors.forename: Denise R
authors.initials: DR
authors.lastname: Shaw
authors.forename: Albert F
authors.initials: AF
authors.lastname: LoBuglio
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D002097:C-Reactive Protein / Q000032:analysis; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D003402:Creatine Kinase / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012449:Safety; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D019444:Vaccines, DNA; D002097:C-Reactive Protein; D003402:Creatine Kinase