Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1158/0008-5472.CAN-05-0542

Type

Journal article

Journal

Cancer Res

Publication Date

01/01/2006

Volume

66

Pages

24 - 28

Keywords

Autoantibodies, Humans, Interferon-gamma, Lymphocyte Activation, Membrane Proteins, Receptors, Antigen, T-Cell, Receptors, Cholinergic, Recombinant Fusion Proteins, Rhabdomyosarcoma, T-Cell Antigen Receptor Specificity, T-Lymphocytes, Transduction, Genetic