Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

1 Publication
Redirection of switchable UniCAR T cells against radioresistant cancer cells
Feldmann, A.; Arndt, C.; Bergmann, R.; Berndt, N.; Jureczek, J.; Albert, S.; Lindner, D.; Koristka, S.; Steinbach, J.; Ehninger, G.; Krause, M.; Kurth, I.; Dubrovska, A.; Bachmann, M.;
Introduction: Radiation is a common therapy for solid tumors. Unfortunately there is a high risk for the outgrowth of radioresistant tumor cells against which only limited treatment options exist. We challenged the idea whether or not chimeric antigen receptor (CAR) engineered T lymphocytes could be used as an adjuvant immunotherapy in combination with radiotherapy. Recently, we have established switchable universal CARs (UniCARs) that bind to a short peptide epitope (E5B9) which does not exist on the surface of living cells. UniCAR T cells are exclusively redirected to tumor cells in the presence of a target module (TM) that exhibits the E5B9 epitope and binds to a tumor associated antigen (TAA) on the tumor cell surface.
Materials and Methods: We used different radioresistant sublines of the head and neck cancer cell line Cal33. Gene expression data for certain TAAs were confirmed by flow cytometry. TMs against potential targets were created from the variable domains of monoclonal antibodies, cloned in lentiviral vectors and purified from supernatants of permanently TM producing 3T3 cells. UniCAR T cells were generated by lentiviral transduction.
Results: Radioresistant Cal33 cell lines expressed PSCA, EGFR and CD98. UniCAR TMs were created against these TAAs. Armed with these TMs UniCAR T cells efficiently killed radioresistant Cal33 cells in vitro and in vivo.
Conclusions: Radioresistant tumor cells can efficiently be killed by redirecting UniCAR T cells against PSCA, CD98 and EGFR and thus resistance to radiotherapy can be overcome by immunotherapy based on the UniCAR technology to these targets.
Keywords: Antibodies, Engineering of antibodies and nanobodies, Immunotherapy
  • Poster
    5th European Congress of Immunology, 02.-05.09.2018, Amsterdam, Niederlande

Publ.-Id: 27446 - Permalink