"Cancer is a devastating disease that affected close family members when I was growing up. At that time, the promises of genetic engineering could not bring much help regarding how to "fix cancer", but they did make think about how to make us stronger against cancer. As we know vaccines do make us stronger against infections. So, I got fascinated about the idea that vaccines also make us stronger against cancer".
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.
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.
Prof. Dr. Renata Stripecke
Hannover Medical School
Carl-Neuberg-Strasse 1 - OE6860
Hans Borst Zentrum Room 6100
D-30625 Hannover – GERMANY
- Lentivirus-induced dendritic cells for immunization against high-risk WT1(+) acute myeloid leukemia. Hum Gene Ther. 2013 Feb;24(2):220-37.
- Integrase-defective lentiviral vectors encoding cytokines induce differentiation of human dendritic cells and stimulate multivalent immune responses in vitro and in vivo. Vaccine. 2012 Jul 20;30(34):5118-31.
- Identity, potency, in vivo viability, and scaling up production of lentiviral vector-induced dendritic cells for melanoma immunotherapy. Hum Gene Ther Methods. 2012 Feb;23(1):38-55.
- Preconditioning therapy with lentiviral vector-programmed dendritic cells accelerates the homeostatic expansion of antigen-reactive human T cells in NOD.Rag1-/-.IL-2rγc-/- mice. Hum Gene Ther. 2011 Oct;22(10):1209-24.
- Lentiviral vectors for induction of self-differentiation and conditional ablation of dendritic cells. Gene Ther. 2011 Aug;18(8):750-64.