Summary

Engineering T cells for cell-based tumor immunotherapy

We study novel approaches to engineer T cells with marker antigens for redirection of T cells using bispecific antibodies (Kobold et al. Selective bispecific T cell recruiting antibody and antitumor activity of adoptive T cell transfer. J Nat Cancer Inst 2015), with PD1-CD28 fusion proteins for protection against T cell suppression by PD-L1-expressing tumor cells (Kobold et al. Impact of a new fusion receptor on PD-1-mediated immunosuppression in adoptive T cell therapy. J Nat Cancer Inst 2015; 107) and with chemokine receptors to direct T cells into tumors (Rapp et al. C-C chemokine receptor type-4 transduction of T cells enhances interaction with dendritic cells, tumor infiltration and therapeutic efficacy of adoptive T cell transfer. Oncoimmunology 2016). We could demonstrate that CD16-based T cell activating receptors can be introduced into T cells and trigger tumor-directed T cell activation. We are currently investigating the potential of different chemokine receptors to redirect cytotoxic T cells into tumors. A second focus is on the design and validation of fusion proteins to be transduced into T cells which can be triggered by bispecific antibodies for MHC-unrestricted tumor cell lysis.

The projects are embedded in the doctorate program i-Target: Immunotargeting of Cancer (2014 bis 2022) of the Elitenetzwerk Bayern (www.immunotarget.de) and in the EU-funded Marie-Sklodowska Curie Network IMMUTRAIN (2016 bis 2020), both lead by our divison.