A novel ex vivo isolation and expansion procedure for chimeric antigen receptor engrafted human T cells.
Genetically engineered T lymphocytes are a promising option for cancer therapy. Prior to adoptive transfer they have to be expanded in vitro to reach therapeutically sufficient numbers. So far, no universal method exists for selective in vitro expansion of engineered T lymphocytes. In order to overcome this problem and for proof of concept we incorporated a novel unique peptide sequence of ten amino acids as epitope (E-Tag) into the binding domains of two novel chimeric antigen receptors (ECARs) directed against either prostate stem cell antigen (PSCA) for the treatment of prostate cancer (PCa) or CD33 for the treatment of acute myeloide leukemia (AML). The epitope tag then was utilized for expanding ECAR engrafted T cells by triggering the modified T cells via a monoclonal antibody directed against the E-Tag (Emab). Moreover, the E-Tag served as an efficient selection epitope for immunomagnetic isolation of modified T cells to high purity. ECAR engrafted T cells were fully functional and mediated profound anti-tumor effects in the respective models of PCa or AML both in vitro and in vivo. The method can be integrated straightforward into clinical protocols to improve therapeutic efficiency of tumor treatment with CAR modified T lymphocytes.
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany; Helmholtz Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radioimmunology, Dresden, Germany.
Marc
M
Cartellieri
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Stefanie
S
Koristka
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Claudia
C
Arndt
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany; Helmholtz Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radioimmunology, Dresden, Germany.
Anja
A
Feldmann
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Slava
S
Stamova
Medical Clinic and Polyclinic I, University Hospital 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Malte
M
von Bonin
Department of Neurosurgery, Section Experimental Neurosurgery and Tumor Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Katrin
K
Töpfer
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Thomas
T
Krüger
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Mathias
M
Geib
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Irene
I
Michalk
Department of Neurosurgery, Section Experimental Neurosurgery and Tumor Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Achim
A
Temme
Medical Clinic and Polyclinic I, University Hospital 'Carl Gustav Carus', TU Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden, TU Dresden, Dresden, Germany.
Martin
M
Bornhäuser
Institute of Virology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden, TU Dresden, Dresden, Germany.
Dirk
D
Lindemann
Medical Clinic and Polyclinic I, University Hospital 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
Gerhard
G
Ehninger
Institute of Immunology, Medical Faculty 'Carl Gustav Carus', TU Dresden, Dresden, Germany; Helmholtz Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radioimmunology, Dresden, Germany; Center for Regenerative Therapies Dresden, TU Dresden, Dresden, Germany.
Michael P
MP
Bachmann
D019264:Adoptive Transfer; D000939:Epitopes; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D011946:Receptors, Antigen / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D011946:Receptors, Antigen