Blankenstein Lab

The development of cancer models that better resemble human cancer.

 

 

The role of the tumor stroma for tumor progression and as target for immunotherapy.

 

 

The development of strategies for convenient and effective T-cell therapy.

 

For clinical application, we employ T cell receptor (TCR) gene therapy. Therefore, we developed humanized TCRab gene loci/HLA trangenic mice that allow isolation of human TCRs against tumor-associated antigens from the non-tolerant repertoire. TCRs derived from these mice are restricted for self-MHC molecules and recognize the human self-antigen as foreign. Thus, T cells expressing such TCR resemble those that naturally protect us from pathogens; this is why we think they have an “optimal” affinity. A first clinical trial with a TCRs from thr humanized mice is in preparation.

 

Most of the current experimental cancer models do not reflect the pathophysiology of real-life cancer. Cancer usually occurs sporadically and is clonal in origin. Between tumor initiation and progression clinically unapparent pre-malignant cells may persist for years or decades in humans. More recently, mouse models of sporadic cancer have been developed. The mouse germ-line can be engineered with high precision so that defined genes can be switched on and off in the adult organism, ideally in a locally and timely controlled fashion. However, analysis of the immune response against sporadic tumors requires the knowledge of a tumor antigen.