Simon-Keller, K., Paschen, A., Eichmueller, S., Gattenloehner, S., Barth, S., Koscielniak, E., Leuschner, I., Stoebel, P., Hombach, A., Abken, H. and Marx, A. (2010). Adoptive T-cell therapy of rhabdomyosarcoma. Pathologe, 31. S. 215 - 221. NEW YORK: SPRINGER. ISSN 0172-8113
Full text not available from this repository.Abstract
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 zeta 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 zeta signalling CAR (chimeric antigen receptor) for redirecting T-cells. T-cells were successfully engineered with the second generation AChRspecific 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.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-496158 | ||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1007/s00292-010-1344-8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Pathologe | ||||||||||||||||||||||||||||||||||||||||||||||||
| Volume: | 31 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Page Range: | S. 215 - 221 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Date: | 2010 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | SPRINGER | ||||||||||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | NEW YORK | ||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 0172-8113 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Language: | German | ||||||||||||||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/49615 |
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