Focus of Research Program

Rational genetic reprogramming for development of cellular vaccines

Dendritic cells (DCs) are professional antigen presenting cells (APCs) that play fundamental role in the development, regeneration and memory of immunity. DCs often become dysfunctional APCs during evolution of chronic diseases, and thus therapeutic approaches to revert their function are warranted. Our laboratory develops new concepts of DC genetic reprogramming based on combining the expression of transgenes genes needed to promote differentiation and activation of DC for clinical use.

Preclinical validation of human vaccines in vitro and in humanized mouse models

One relevant pre-requisite for approval of human DC vaccines for use in humans is to demonstrate their potency and safety in cell culture systems or in animal models. Experimental in vitro assays based on stimulation of human T cells for antigen-specific responses and humanized mouse models have been established in our laboratory. Along with the validation process for future clinical use, these novel experimental systems enable technologies for testing different types of vaccines.

Clinical development

We have shown that human DC precursors (monocytes) can be effectively genetically reprogrammed with designed lentiviral vectors co-expressing combinations of genes (cytokines and antigens) resulting in induced DCs (iDCs). These highly viable disease-specific APCs can be produced under clinically compliant conditions in just one day of ex vivo culture. Clinical development under good-manufacturing practices of iDC vaccines is ongoing for autologous immune therapy against cancer and as allogeneic "donor DC infusion" for treatment of patients after stem cell transplantation.