In vitro development of dendritic cells to stimulate WT1 specific lymphocyte

• Grant number: 05/00680-5
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2005
• End date: August 31, 2007
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Simone Cristina Olenscki Gilli
• Grantee: Simone Cristina Olenscki Gilli
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The demonstration that even bulky invasive tumours can undergo complete remission under appropriate immune stimulation has shown it is indeed possible to treat cancer successfully by immune manipulation. The recent discoveries of tumour antigens and the development of efficient methods to generate in vitro specific anti-tumour immune cells increased the successfull immune and clinical responses of the immunotherapy to the treatment of human cancer. The central role of dendritic cells in the immune response suggests its great potencial in the development of immunotherapeutic vaccines that can break immunologic tolerance against specific tumour antigens. Among the tumour antigens identified, the protein WT1, overexpressed in many types of neoplasies and capable to induce a specific immune response in vitro and in vivo, can be distinguished. The objective of this project is to define an efficient, safe and economic method to produce mature dendritic cells in vitro carrying WT1 derived antigens and to evaluate the possibility to use this cells as immunotherapeutic vaccines against human neoplasies. The dendritic cells will be produced from mononuclear cells obtained of the peripheral blood and will be evaluated its morphological characteristics, the superficial cellular markers expression and the production of specific cytokines. The messenger RNA and a sinthetic peptide, both derived from WT1 protein, will be incorporated to dendritic cells as an antigen. Lymphoproliferation and cytotoxicity essays will be performed to observe the capacity of the dendritic cells to stimulate a specific immune response. (AU)