Targeting self-antigens through allogeneic TCR gene transfer

Adoptive transfer of T-cell receptor (TCR) genes has been proposed as an attractive approach for immunotherapy in cases where the endogenous T-cell repertoire is insufficient. While there are promising data demonstrating the capacity of TCR-modified T cells to react to foreign antigen encounter, the...

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Bibliographic Details
Published in:Blood 2006-08, Vol.108 (3), p.870-877
Main Authors: de Witte, Moniek A., Coccoris, Miriam, Wolkers, Monika C., van den Boom, Marly D., Mesman, Elly M., Song, Ji-Ying, van der Valk, Martin, Haanen, John B.A.G., Schumacher, Ton N.M.
Format: Article
Language:English
Subjects:
Adoptive Transfer - methods
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Antigens, Neoplasm - immunology
Applied cell therapy and gene therapy
Autoantigens - immunology
Biological and medical sciences
Graft vs Host Disease
Immunotherapy - methods
Major Histocompatibility Complex
Medical sciences
Melanoma, Experimental - therapy
Mice
Mice, Inbred C57BL
Receptors, Antigen, T-Cell - administration & dosage
Receptors, Antigen, T-Cell - genetics
T-Lymphocytes - metabolism
T-Lymphocytes - transplantation
Transduction, Genetic
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Transplantation, Homologous
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Summary:Adoptive transfer of T-cell receptor (TCR) genes has been proposed as an attractive approach for immunotherapy in cases where the endogenous T-cell repertoire is insufficient. While there are promising data demonstrating the capacity of TCR-modified T cells to react to foreign antigen encounter, the feasibility of targeting tumor-associated self-antigens has not been addressed. Here we demonstrate that T-cell receptor gene transfer allows the induction of defined self-antigen–specific T-cell responses, even when the endogenous T-cell repertoire is nonreactive. Furthermore, we show that adoptive transfer of T-cell receptor genes can be used to induce strong antigen-specific T-cell responsiveness in partially MHC-mismatched hosts without detectable graft versus host disease. These results demonstrate the feasibility of using a collection of “off the shelf” T-cell receptor genes to target defined tumor-associated self-antigens and thereby form a clear incentive to test this immunotherapeutic approach in a clinical setting.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-08-009357