Evaluation of natural killer (NK) cells expanded ex vivo for treatment of ovarian carcinoma

• Grant number: 06/04900-2
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2007
• End date: July 31, 2009
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Fernando Guimarães
• Grantee: Fernando Guimarães
• Host Institution: Centro de Atenção Integral à Saúde da Mulher (CAISM). Hospital da Mulher Professor Doutor José Aristodemo Pinotti. Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

This project aimed at evaluating the therapeutic potential of NK cell-enriched effector cell preparations for treatment of ovarian carcinoma. The diffuse nature of this disease and quick metastatic spread throughout the peritoneal cavity impair the treatment effectiveness, currently based on surgery and chemotherapy. New therapeutic approaches to eliminate tumor cells and prevent relapse are need. Recent progress on the comprehension of the signalling pathways involved in cytotoxic activation of the NK cells against cancer together with new methods for obtaining larger amounts of these cells have opened up new therapeutic possibilities. Therefore, this project was inspired on recent studies carried out at Karolinska Institute (author’s post-doc) showing the feasibility of expanding human NK cells for cancer treatment. In the present study, NK cell-enriched effector cell preparations will be obtained by ex vivo selective expansion, whereas mononuclear cells taken from peripheral blood and ascite of ovarian carcinoma patients are exposed to IL-2 for a long period. A whole of twelve patients (6 presenting epithelial ovarian carcinoma and 6 presenting benign lesions) will be sampled. Cell phenotyping will be performed during ex vivo selective expansion of NK cells. Anti-tumor activity of the enriched NK cell preparations will be evaluated against tumor cell lines. Whenever possible, the anti-tumor activity of the enriched NK cell preparations will also be evaluated against primary autologous ovarian carcinoma tumor cells. Thus, primary cultures of ovarian carcinomas cells will be performed using fragments of tumors taken during the surgery for ovarian cancer diagnosis. The procedures for NK cell expansion and primary cultures of ovarian carcinomas cells were recently set in the institution hosting the study and preliminary data showing the feasibility of the method for NK cell expansion have just started being obtained. Future results will be analyzed using nonparametric statistics (Mann-Whitney U test, P<0.05), allowing to evaluate effectiveness of the expansion method, as well as, anti-tumor activity of the enriched NK cell preparation. The application budget includes funds for acquisition of reagents and plastic material necessary for cell culturing, phenotyping and evaluation of the anti-tumor activity. Besides, it also includes equipments to improve laboratory facilities in order to better process human lymphocytes separation and culturing. (AU)