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Blood Cancer J. 2015 Sep 18;5:e348. doi: 10.1038/bcj.2015.73.

Bispecific antibody releasing-mesenchymal stromal cell machinery for retargeting T cells towards acute myeloid leukemia blasts.

Author information

1
Department of Tumor-/Radioimmunology, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
2
University Cancer Center (UCC), Technical University Dresden, Tumorimmunology, Dresden, Germany.
3
Cellex Patient Treatment GmbH, Dresden, Germany.
4
Medical Clinic and Polyclinic I, University Hospital 'Carl Gustav Carus', Technical University Dresden, Dresden, Germany.
5
GEMoaB Monoclonals GmbH, Blasewitzer Strasse 41, Dresden, Germany.
6
DFG-Center for Regenerative Therapies Dresden, Technical University Dresden, Dresden, Germany.

Abstract

Bispecific antibodies (bsAbs) engaging T cells are emerging as a promising immunotherapeutic tool for the treatment of hematologic malignancies. Because their low molecular mass, bsAbs have short half-lives. To achieve clinical responses, they have to be infused into patients continously, for a long period of time. As a valid alternative we examined the use of mesenchymal stromal cells (MSCs) as autonomous cellular machines for the constant production of a recently described, fully humanized anti-CD33-anti-CD3 bsAb, which is capable of redirecting human T cells against CD33-expressing leukemic cells. The immortalized human MSC line SCP-1 was genetically modified into expressing bsAb at sufficient amounts to redirect T cells efficiently against CD33 presenting target cells, both in vitro and in an immunodeficient mouse model. Moreover, T cells of patients suffering from acute myeloid leukemia (AML) in blast crisis eliminated autologous leukemic cells in the presence of the bsAb secreting MSCs over time. The immune response against AML cells could be enhanced further by providing T cells an additional co-stimulus via the CD137-CD137 ligand axis through CD137L expression on MSCs. This study demonstrates that MSCs have the potential to be used as cellular production machines for bsAb-based tumor immunotherapy in the future.

PMID:
26383821
PMCID:
PMC4648523
DOI:
10.1038/bcj.2015.73
[Indexed for MEDLINE]
Free PMC Article

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