Retargeting of UniCAR T cells with an in vivo synthesized target module directed against CD19 positive tumor cells

Oncotarget
Dominik BachmannMichael Bachmann

Abstract

Recent treatments of leukemias with T cells expressing chimeric antigen receptors (CARs) underline their impressive therapeutic potential but also their risk of severe side effects including cytokine release storms and tumor lysis syndrome. In case of cross-reactivities, CAR T cells may also attack healthy tissues. To overcome these limitations, we previously established a switchable CAR platform technology termed UniCAR. UniCARs are not directed against typical tumor-associated antigens (TAAs) but instead against a unique peptide epitope: Fusion of this peptide epitope to a recombinant antibody domain results in a target module (TM). TMs can cross-link UniCAR T cells with tumor cells and thereby lead to their destruction. So far, we constructed TMs with a short half-life. The fast turnover of such a TM allows to rapidly interrupt the treatment in case severe side effects occur. After elimination of most of the tumor cells, however, longer lasting TMs which have not to be applied via continous infusion would be more convenient for the patient. Here we describe and characterize a TM for retargeting UniCAR T cells to CD19 positive tumor cells. Moreover, we show that the TM can efficiently be produced in vivo from producer cells h...Continue Reading

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Citations

Aug 16, 2019·Cancer Immunology, Immunotherapy : CII·Stefanie KoristkaMichael P Bachmann
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Mar 23, 2021·Oncotarget·Ralf BergmannAnnette G Beck-Sickinger
Apr 4, 2021·International Journal of Molecular Sciences·Nicole BerndtMichael P Bachmann

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Methods Mentioned

BETA
immunodepletion
flow cytometry
ELISA
transfection
enzyme-linked immunosorbent assay
FACS
X-ray

Software Mentioned

MACSQuantify ®
UniCAR
MACSQuantify
UniCARs
MACSQuant Analyzer
GraphPad Prism
MACSQuant
GraphPad

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