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

• Published in: Haematologica (Roma) Vol. 96; no. 3; pp. 477 - 481
• Main Authors: VAN LOENEN, Marleen M, DE BOER, Renate, HAGEDOORN, Renate S, VAN EGMOND, Esther H. M, FREDERIK FALKENBURG, J. H, HEEMSKERK, Mirjam H. M
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01-03-2011
• Subjects: Biological and medical sciences; Brief Report; Clinical trials; Gene therapy; Genes, T-Cell Receptor - genetics; Genes, T-Cell Receptor - immunology; Genetic Therapy - methods; Hematologic and hematopoietic diseases; Hematologic Neoplasms - genetics; Hematologic Neoplasms - immunology; Hematologic Neoplasms - therapy; Humans; Immunotherapy, Adoptive - methods; Lymphocytes T; Malignancy; Medical sciences; Minor histocompatibility antigens; Minor Histocompatibility Antigens - genetics; Minor Histocompatibility Antigens - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Retroviridae - genetics; Retroviridae - immunology; T-cell receptor; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Transduction, Genetic; T-cell receptors; T cell receptor; Cell therapy; Hematology; gene transfer; TCR optimization; Malignant hemopathy; Optimization; Genetic transfer; Treatment; Gene; T-Lymphocyte; Genetics; Adoptive immunization; adoptive immunotherapy; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2010.025916

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.