Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Gattenlohner, S; Marx, A; Markfort, B; Pscherer, S; Landmeier, S; Juergens, H; Muller-Hermelink, HK; Matthews, I; Beeson, D; Vincent, A; Rossig, C.
Rhabdomyosarcoma lysis by T cells expressing a human autoantibody-based chimeric receptor targeting the fetal acetylcholine receptor.
Cancer Res. 2006; 66(1):24-28
Doi: 10.1158/0008-5472.CAN-05-0542
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- Leading authors Med Uni Graz
- Gattenlöhner Stefan
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- Abstract:
- Rhabdomyosarcomas are the most frequent malignant soft tissue tumors of childhood; however, because current multimodality treatments fail to improve the poor survival rate of children with metastatic rhabdomyosarcoma, new treatments are required. We previously identified the gamma-subunit of the fetal acetylcholine receptor (fAChR) as a specific cell surface target in rhabdomyosarcoma. Here, we engineered human T lymphocytes to express chimeric receptors composed of the antigen-binding domain of a human anti-fAChR antibody joined to the signaling domain of the human T-cell receptor zeta-chain. The interaction of fAChRzeta-transduced T cells with fAChR-positive rhabdomyosarcoma cell lines, but not with fAChR-negative control cells, induced T-cell activation characterized by strong secretion of IFN-gamma and delayed lysis of tumor cells. Importantly, we found that in six of six rhabdomyosarcoma patients, chemotherapy increased fAChR expression on residual tumor cells in vivo. Our observations suggest that these fully human chimeric fAChRzeta-transduced T cells, which should be well tolerated by the patient, have potential use in vivo both as a primary treatment for rhabdomyosarcoma and as a complementary approach to eradicate residual tumor cells after chemotherapy.
- Find related publications in this database (using NLM MeSH Indexing)
- Autoantibodies - biosynthesis Autoantibodies - immunology
- Humans -
- Interferon-gamma - biosynthesis Interferon-gamma - immunology Interferon-gamma - secretion
- Lymphocyte Activation - immunology
- Membrane Proteins - biosynthesis Membrane Proteins - genetics Membrane Proteins - immunology
- Receptors, Antigen, T-Cell - biosynthesis Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology
- Receptors, Cholinergic - biosynthesis Receptors, Cholinergic - genetics Receptors, Cholinergic - immunology
- Recombinant Fusion Proteins - biosynthesis Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology
- Rhabdomyosarcoma - drug therapy Rhabdomyosarcoma - genetics Rhabdomyosarcoma - immunology Rhabdomyosarcoma - metabolism
- T-Cell Antigen Receptor Specificity - immunology
- T-Lymphocytes - immunology
- Transduction, Genetic -