Optimization of the HA-1-specific T-cell receptor for gene therapy of hematologic malignancies.
To broaden the applicability of adoptive T-cell therapy for the treatment of hematologic malignancies, we aim to start a clinical trial using HA-1-TCR transferred virus-specific T cells. TCRs directed against the minor histocompatibility antigen (MiHA) HA-1 are good candidates for TCR gene transfer to treat hematologic malignancies because of the hematopoiesis-restricted expression and favorable frequency of HA-1. For optimal anti-leukemic reactivity, high cell-surface expression of the introduced TCR is important. Previously, however, we have demonstrated that gene transferred HA-1-TCRs are poorly expressed at the cell-surface. In this study several strategies were explored to improve expression of transferred HA-1-TCRs.
Department of Hematology, Leiden University Medical Center C2-R, PO Box 9600 2300 RC Leiden, The Netherlands. m.m.van_loenen@lumc.nl
Marleen M
MM
van Loenen
Renate
R
de Boer
Renate S
RS
Hagedoorn
Esther H M
EH
van Egmond
J H Frederik
JH
Falkenburg
Mirjam H M
MH
Heemskerk
D019672:Genes, T-Cell Receptor / Q000235:genetics* / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D014161:Transduction, Genetic
D015778:Minor Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell