CELLULAR VACCINES

This project is devoted to the development of novel cellular vaccines designed to treat cancer patients. These cellular vaccines present and enhance immunogens, which will elicit a potent immune response. The g oal is to achieve safe and effective immune reaction against the patie nt's own tumour. (1) Autologous cellular vaccines are prepared by proc essing circulating brood mononuclear cells outside of the patient's bo dy (ex vivo) to differentiate them into antigen-presenting cells (APCs ). Monocyte-derived APCs (MD-APCs) are then grown in the presence of e xogenous target antigens (tumour cell debris, or apoptotic bodies) to become fully mature APCs. (2) Functionality for antigen presentation t o T cells of ex vivo MD-APCs is evaluated in vivo. (3) Cellular vaccin es are tested in selected rodent animal models. Efficiency and immune response are monitored in pertinent experimental systems for cancer. P harmacological data are generated for clinical investigation. Toleranc e and biologic effects are documented in primates. (4) The first clini cal trials on cancer patients are taking place in 1998 on melanoma and prostate cancer to validate the concept. Specialized eel processors w ith dedicated software and standardized controls are being developed a nd used for the preparation of cellular vaccines. (5) The evaluation o f new non-viral vectors and the validation of new non-viral transfecti on methods of mononuclear cells with marker genes is in progress and w ill lead to the ex vivo transfection of genes coding for immunostimula ting cytokines or for tumour antigens in MD-APCs. Efficiency will be v alidated in vitro and in animal models. The ex vivo and animal model s tudies validate the clinical relevance of this new cellular immunotech nology. Clinical validation of individual autologous cellular vaccines in specific indications for which no treatment is presently available will allow the development of cellular and gene immunotherapy for oth er types of cancers.