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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Adoptive T-cell therapy of rhabdomyosarcoma; [Adoptive T-Zell-Therapie des Rhabdomyosarkoms]
Pathologe, Volume 31, No. SUPPL. 2, Year 2010
Notification
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Description
Aims. To improve survival of patients with advanced rhabdomyosarcomas (RMS), we aimed to adoptively transfer T-cells with redirected specificity for the fetal acetylcholine receptor (AChR), an RMS-specific cell surface antigen.Methods. A "second generation" chimeric antigen receptor (CAR) with a combined CD28-CD3 signaling domain was derived from our previously described chimeric antigen receptor composed of an extracellular human anti-fAChR antibody fragment, an Fc hinge region, and the intracellular T-cell receptor zeta chain. Lymphocytes from the peripheral blood were modified by retroviral transduction and monitored by FACS analysis. Cytotoxicity of modified T-cells towards RMS cells was recorded by MTT-based viability tests; expression of co-stimulatory molecules and anti-apoptotic genes was studied by FACS and qRT-PCR analysis.Results. Co-stimulatory molecules were expressed in low levels on RMS cells giving the rationale to generate a CD28-CD3 signalling CAR (chimeric antigen receptor) for redirecting T-cells. T-cells were successfully engineered with the "second generation" AChR-specific chimeric antigen receptor. Despite of high CAR expression engineered T-cells showed low killing efficiency towards RMS compared to redirected killing of CD20+ lymphoma or CEA-expressing adenocarcinoma cell lines when redirected by CD20- and/or CEA-specific CAR.Conclusions. Data suggest that RMS cells exhibit resistance to a T-cell attack redirected by a fAChR-specific CAR. Inhibition of anti-apoptotic pathways in those cells may improve sensitivity to conventional as well as T-cell-based therapeutics. © Springer-Verlag 2010.
Authors & Co-Authors
Eichmüller, Stefan B.
Germany, Heidelberg
German Cancer Research Center
Gattenlöhner, Stefan
Austria, Graz
Medizinische Universität Graz
Barth, Stefan W.
Unknown Affiliation
Kościelniak, Ewa
Germany, Stuttgart
Klinikum Stuttgart Olgahospital
Leuschner, Ivo
Germany, Kiel
Universitätsklinikum Schleswig-holstein Campus Kiel
Abken, Hinrich
Unknown Affiliation
Marx, Alexander H.
Germany, Heidelberg
Universität Heidelberg
Statistics
Citations: 5
Authors: 7
Affiliations: 6
Identifiers
Doi:
10.1007/s00292-010-1344-8
ISSN:
01728113