Selecting highly affine and well-expressed TCRs for gene therapy of melanoma.

Détails

ID Serval
serval:BIB_DFECE8B72CF3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Selecting highly affine and well-expressed TCRs for gene therapy of melanoma.
Périodique
Blood
Auteur⸱e⸱s
Jorritsma A., Gomez-Eerland R., Dokter M., van de Kasteele W., Zoet Y.M., Doxiadis I.I., Rufer N., Romero P., Morgan R.A., Schumacher T.N., Haanen J.B.
ISSN
0006-4971
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
110
Numéro
10
Pages
3564-72
Langue
anglais
Notes
Publication types: Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
A recent phase 1 trial has demonstrated that the generation of tumor-reactive T lymphocytes by transfer of specific T-cell receptor (TCR) genes into autologous lymphocytes is feasible. However, compared with results obtained by infusion of tumor-infiltrating lymphocytes, the response rate observed in this first TCR gene therapy trial is low. One strategy that is likely to enhance the success rate of TCR gene therapy is the use of tumor-reactive TCRs with a higher capacity for tumor cell recognition. We therefore sought to develop standardized procedures for the selection of well-expressed, high-affinity, and safe human TCRs. Here we show that TCR surface expression can be improved by modification of TCR alpha and beta sequences and that such improvement has a marked effect on the in vivo function of TCR gene-modified T cells. From a panel of human, melanoma-reactive TCRs we subsequently selected the TCR with the highest affinity. Furthermore, a generally applicable assay was used to assess the lack of alloreactivity of this TCR against a large series of common human leukocyte antigen alleles. The procedures described in this study should be of general value for the selection of well- and stably expressed, high-affinity, and safe human TCRs for subsequent clinical testing.
Mots-clé
Animals, Female, Gene Expression Regulation, Neoplastic, Gene Therapy, Gene Transfer Techniques, Humans, Immunotherapy, Adoptive, Jurkat Cells, K562 Cells, Melanoma, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, Substrate Specificity, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 12:27
Dernière modification de la notice
20/08/2019 17:04
Données d'usage