Optimization of the HA-1-specific T-cell receptor for gene therapy of hematologic malignancies.

Abstract

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.

• Authors: Marleen M van Loenen, Renate de Boer, Renate S Hagedoorn, Esther H M van Egmond, J H Frederik Falkenburg, Mirjam H M Heemskerk
• Journal: Haematologica (Haematologica) Vol. 96 Issue 3 Pg. 477-81 (Mar 2011) ISSN: 1592-8721 [Electronic] Italy
• PMID: 21109688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Minor Histocompatibility Antigens
• Receptors, Antigen, T-Cell

Topics

• Genes, T-Cell Receptor (genetics, immunology)
• Genetic Therapy (methods)
• Hematologic Neoplasms (genetics, immunology, therapy)
• Humans
• Immunotherapy, Adoptive (methods)
• Minor Histocompatibility Antigens (genetics, immunology)
• Receptors, Antigen, T-Cell (genetics, immunology)
• Retroviridae (genetics, immunology)
• T-Lymphocytes (cytology, immunology)
• Transduction, Genetic