A novel ex vivo isolation and expansion procedure for chimeric antigen receptor engrafted human T cells

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Article numbere93745
JournalPLoS ONE
Volume9
Issue number4
Publication statusPublished - 2014
Peer-reviewedYes

External IDs

Scopus 84899432342
researchoutputwizard legacy.publication#61726
PubMed 24699869
PubMedCentral PMC3974878
researchoutputwizard legacy.publication#61219
researchoutputwizard legacy.publication#61647
ORCID /0000-0002-0320-4223/work/151983047

Keywords

Keywords

  • Adoptive Transfer, Epitopes, Humans, Lymphocyte Activation/immunology, Receptors, Antigen/genetics, T-Lymphocytes/immunology