A theranostic PSMA ligand for PET imaging and retargeting of T cells expressing the universal chimeric antigen receptor UniCAR

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Claudia Arndt - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Anja Feldmann - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Stefanie Koristka - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Martin Schäfer - , German Cancer Research Center (DKFZ) (Author)
  • Ralf Bergmann - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Nicola Mitwasi - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Nicole Berndt - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Dominik Bachmann - , University Cancer Center (UCC) (Author)
  • Alexandra Kegler - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Marc Schmitz - , Institute for Immunology (Author)
  • Edinson Puentes-Cala - , Corporación para la Investigación de la Corrosión (CIC) (Author)
  • Javier Andrés Soto - , Universidad de Santander (Author)
  • Gerhard Ehninger - , GEMoaB Monoclonals GmbH (Author)
  • Jens Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Christos Liolios - , German Cancer Research Center (DKFZ) (Author)
  • Gerd Wunderlich - , Klinik für Nuklearmedizin (Author)
  • Jörg Kotzerke - , Department of Nuclear Medicine, National Center for Tumor Diseases (Partners: UKD, MFD, HZDR, DKFZ), Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Klaus Kopka - , German Cancer Consortium (Partner: DKTK, DKFZ), German Cancer Research Center (DKFZ) (Author)
  • Michael Bachmann - , German Cancer Consortium (Partner: DKTK, DKFZ), University Cancer Centre, Helmholtz-Zentrum Dresden-Rossendorf, German Cancer Research Center (DKFZ) (Author)

Abstract

Chimeric antigen receptor (CAR) T cells have shown impressive therapeutic potential. Due to the lack of direct control mechanisms, therapy-related adverse reactions including cytokine release- and tumor lysis syndrome can even become life-threatening. In case of target antigen expression on non-malignant cells, CAR T cells can also attack healthy tissues. To overcome such side effects, we have established a modular CAR platform termed UniCAR: UniCAR T cells per se are inert as they recognize a peptide epitope (UniCAR epitope) that is not accessible on the surface of living cells. Bifunctional adapter molecules termed target modules (TM) can cross-link UniCAR T cells with target cells. In the absence of TMs, UniCAR T cells automatically turn off. Until now, all UniCAR TMs were constructed by fusion of the UniCAR epitope to an antibody domain. To open up the wide field of low-molecular-weight compounds for retargeting of UniCAR T cells to tumor cells, and to follow in parallel the progress of UniCAR T cell therapy by PET imaging we challenged the idea to convert a PET tracer into a UniCAR-TM. For proof of concept, we selected the clinically used PET tracer PSMA-11, which binds to the prostate-specific membrane antigen overexpressed in prostate carcinoma. Here we show that fusion of the UniCAR epitope to PSMA-11 results in a low-molecular-weight theranostic compound that can be used for both retargeting of UniCAR T cells to tumor cells, and for non-invasive PET imaging and thus represents a member of a novel class of theranostics.

Details

Original languageEnglish
Pages (from-to)1659095
JournalOncoimmunology
Volume8
Issue number11
Publication statusPublished - 2019
Peer-reviewedYes

External IDs

PubMedCentral PMC6791425
Scopus 85072036449

Keywords