Michael Hudecek: CAR T-cell Engineering
Our group is working in the field of tumor immunology and our efforts are directed at the development and clinical translation of adoptive immunotherapy of cancer with tumor-specific T cells. A recent focus in the lab is the engineering of T cells that have been modified by gene transfer to express tumor-targeting chimeric antigen receptors (CARs). CARs are synthetic receptors with an extracellular antigen-binding domain derived from the variable heavy and light chains of a monoclonal antibody and an intracellular signaling module that mediates T-cell activation after antigen-binding. We are working on defining target molecules that are expressed on malignant cells but not on vital normal tissues and can be targeted by CAR T cells, and deriving insights into how to best design these receptors in order to confer optimum tumor recognition and T-cell activation.
Receptor affinity and extracellular domain modifications affect tumor-recognition by ROR1-specific chimeric antigen receptor T cells. Hudecek M, Lupo-Stanghellini MT, Kosasih P, Sommermeyer D, Jensen MC, Rader C, Riddell SR. Clin Cancer Res. 2013 Jun 15;19(12):3153-3164.
The B-cell tumor-associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor. Hudecek M, Schmitt TM, Baskar S, Lupo-Stanghellini MT, Nishida T, Yamamoto TN, Bleakley M, Turtle CJ, Chang WC, Greisman HA, Wood B, Maloney DG, Jensen MC, Rader C, Riddell SR. Blood. 2010 Nov 25;116(22):4532.
Adoptive T-cell therapy for B-cell malignancies. Hudecek M, Anderson LD Jr, Nishida T, Riddell SR. Expert Rev Hematol. 2009 Oct;2(5):517-32.