Evaluation of immunological responses in patients with ovarian cancer treated with the anti-idiotype vaccine ACA125 by determination of intracellularcytokines - 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 CA12 5 expressed by most malignant ovarian tumors. Patients with CA125-positive tumors are immunologically tolerant to CA125, which could be overcome by th e use of an anti-idiotypic antibody as a surrogate for the tumor antigen CA 125. An immunological response to the anti-idiotype ACA125 in these patient s was associated with a statistically significant survival prolongation. Hu moral immunity to ACA125 was assessed by induction of anti-anti-idiotypic a ntibodies (Ab3) directed against CA125, Using flow cytometric detection met hods 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 f or a Th1 cell type immune response after treatment with ACA125, A delayed i nduction 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 eff ective immunotherapy with anti-idiotype vaccines.