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Title: A theranostic PSMA ligand for PET imaging and retargeting of T cells expressing the universal chimeric antigen receptor UniCAR
Authors: Arndt, Claudia
Feldmann, Anja
Koristka, Stefanie
Schäfer, Martin
Bergmann, Ralf
Mitwasi, Nicola
Berndt, Nicole
Bachmann, Dominik
Kegler, Alexandra
Schmitz, Marc
Puentes-Cala, Edinson
Soto, Javier-Andrés
Ehninger, Gerhard
Pietzsch, Jens
Liolios, Christos
Wunderlich, Gerd
Kotzerke, Jörg
Kopka, Klaus
Bachmann, Michael
Keywords: PSMA ligand
Prostate cancer
PET imaging
Issue Date: 7-Sep-2019
Publisher: Taylor & Francis Group
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.
Description: Digital
Appears in Collections:DCAAA. Artículos de Investigación

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