Evaluation of immunological responses in patients with ovarian cancer treated with the anti-idiotype vaccine ACA125 by determination of intracellular cytokines--a preliminary report.
In a first clinical trial, 45 patients with advanced ovarian carcinoma and recurrences were treated with the murine monoclonal anti-idiotypic antibody (Ab2) designated ACA125 for active immunotherapy. The monoclonal antibody (MAb) ACA125 mimics a specific epitope of the tumor-associated antigen CA125 expressed by most malignant ovarian tumors. Patients with CA125-positive tumors are immunologically tolerant to CA125, which could be overcome by the use of an anti-idiotypic antibody as a surrogate for the tumor antigen CA125. An immunological response to the anti-idiotype ACA125 in these patients was associated with a statistically significant survival prolongation. Humoral immunity to ACA125 was assessed by induction of anti-anti-idiotypic antibodies (Ab3) directed against CA125. Using flow cytometric detection methods we observe alterations of the intracellular cytokines IFN-gamma, IL-2, and IL-4 at the single-cell level during the course of immunization. There was a strong increase of intracellular IFN-gamma and IL-2 characteristic for a Th1 cell type immune response after treatment with ACA125. A delayed induction of Th2 type response, which promotes antibody-mediated immunity by B cells, could also be detected. The understanding of the kinetics of Th1 and Th2 responses could be important to improve treatment schedules for effective immunotherapy with anti-idiotype vaccines.
Reinartz
S
S
Center of Obstetrics and Gynecology, University of Bonn, Germany.
Boerner
H
H
Koehler
S
S
Von Ruecker
A
A
Schlebusch
H
H
Wagner
U
U
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D018394:CA-125 Antigen / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008214:Lymphocytes / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy*
D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D018394:CA-125 Antigen; D019496:Cancer Vaccines; D016207:Cytokines