Immunotherapy of Cervical Cancer

Objective: Cervical cancer presents a unique tumor model system for immunotherapy. Our goal is to develop a system for efficiently generating tumor-specific cytotoxic lymphocytes (CTLs) against human cervical cancers. Material and Methods: Establishing of cervical cancer cell lines from operative specimens. Optimizing the proliferation of CD 8+ T-cells from 3 readily available sources: a) Tumor Infiltrating Lymphocytes (TILs) b) draining lymph nodes c) peripheral blood. Determination of the importance of T-cell source, HLA type, HPV subtype, expression of costimulatory molecules, and role of cytokines (esp. interferons) to establish the minimum criteria for priming cells to effectively stimulate and activate T-cells for the production of tumor-specific CTLs. Developing a cell line as a novel stimulator cell line for T-cells. Thus specific HLA Class I genes could be transfected along with specific HPV E6/E7 expression vectors to produce stimulator cellsarget cells for tumor- specific CTLs. The advantages would be that virtually any combination of HLA and HPV type could be constructed for use in producing CTLs without producing allogenic responses. Studying the impact of enhancing stimulator-effector interactions by taking advantage of known agents. These include interferons, retinoids, and estrogens. Exploring the potential for imiquimod for the enhancement of antigen presentation and CTL production in vitro. Future prospectes: Research activities in the "Immunotherapy of Cervical Cancer" shall be continued in the Gyn/Ob department in Graz/Austria. This basic science work should lead to direct clinical applications within a 3-5 year period.