Genetic engineering of virus-specific T cells with T-cell receptors recognizing minor histocompatibility antigens for clinical application

被引:32
|
作者
Griffioen, Marieke [1 ]
van Egmond, H. M. Esther
Barnby-Porritt, Helen [2 ]
van der Hoorn, Menno A. W. G.
Hagedoorn, Renate S.
Kester, Michel G. D.
Schwabe, Nikolai [2 ]
Willemze, Roel
Falkenburg, J. H. Frederik
Heemskerk, Mirjam H. M.
机构
[1] Leiden Univ, Med Ctr, Dept Hematol, Lab Expt Hematol, NL-2300 RC Leiden, Netherlands
[2] Prolmmune Ltd, Magdalen Ctr, Oxford, England
来源
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2008年 / 93卷 / 10期
关键词
allogeneic stem cell transplantation; immunotherapy; gene therapy; T cell receptor;
D O I
10.3324/haematol.13067
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Donor lymphocyte infusion is an effective form of adoptive immunotherapy for hematologic malignancies after allogeneic stem cell transplantation. Graft-versus-host disease, however, often develops due to recognition of ubiquitously-expressed minor histocompatibility antigens. Transfer of T-cell receptors recognizing hematopoiesis-restricted minor histocompatibility antigens to virus-specific T cells may be a powerful anti-tumor therapy with a low risk of graft-versus-host disease. The purpose of this study was to develop an optimal T-cell receptors-encoding multi-cistronic retroviral vector and an efficient method for generating T-cell receptors-engineered virus-specific T cells. Design and Methods Retroviral vectors encoding the T-cell receptors for the hematopoiesis-restricted minor histocompatibility antigen HA-2 with and without selection markers were compared for T-cell receptors surface expression and HA-2-specific lysis. In addition, two different methods, i.e. peptide stimulation of CD8(+) cells and Pro5 (R) MHC pentamer-based isolation of antigen-specific T cells, were investigated for their efficiency to generate T-cell receptors-transduced virus-specific T cells. Results Bi-cistronic vectors without selection markers most efficiently mediated T-cell receptors surface expression and HA-2-specific lysis. Furthermore, both methods were useful for generating genemodified cells, but the purity of virus-specific T cells was higher after pentamer isolation. Finally, the capacity of gene-modified cells to express the transgenic T-cell receptors at the cell surface markedly differed between virus-specific T cells and was correlated with lysis of relevant target cells. Conclusions Our data support T-cell receptors gene transfer to pentamer-isolated virus-specific T cells using bi-cistronic retroviral vectors and illustrate the relevance of selection of gene-modified T cells with appropriate transgenic T-cell receptors surface expression for clinical gene therapy.
引用
收藏
页码:1535 / 1543
页数:9
相关论文
共 50 条
  • [1] Genetic engineering of virus specific T-cells with T-cell receptors recognising minor histocompatibility antigens for clinical application
    Griffioen, M.
    van Egmond, H. M.
    Barnby-Porritt, H.
    van der Hoorn, M. A. W. G.
    Hagedoorn, R. S.
    Kester, M. G. D.
    Schwabe, N.
    Willemze, R.
    Falkenburg, J. H. F.
    Heemskerk, M. H. M.
    BONE MARROW TRANSPLANTATION, 2008, 41 : S163 - S163
  • [2] COMBINED ISOLATION OF MULTI ANTIGEN SPECIFIC T CELL PRODUCTS CONTAINING NAIVE AND/OR MEMORY VIRUS-SPECIFIC T CELLS AND T CELLS SPECIFIC FOR TUMOR ASSOCIATED AND MINOR HISTOCOMPATIBILITY ANTIGENS
    Roex, M.
    Luna, J. Matamoros
    Hageman, L.
    van Egmond, E.
    Veld, S.
    van Liempt, E.
    Hoogstraten, C.
    Germeroth, L.
    van Balen, P.
    Halkes, S.
    Falkenburg, J. F.
    Jedema, I.
    HAEMATOLOGICA, 2016, 101 : 464 - 464
  • [3] ENGINEERING T CELL TARGETING MINOR HISTOCOMPATIBILITY ANTIGENS
    Masroori, N.
    Minguy, A.
    Sawchyn, C.
    Mathieu, C.
    Trottier, J.
    Bastien, J.
    Sanchez-Dardon, J.
    Dave, V.
    Mallette, F.
    Roy, D.
    CYTOTHERAPY, 2023, 25 (06) : S238 - S239
  • [4] ANTIBODIES TO T-CELL RECEPTORS AND TO HISTOCOMPATIBILITY ANTIGENS
    RAMSEIER, H
    CELLULAR IMMUNOLOGY, 1974, 12 (03) : 422 - 428
  • [5] Regulatory T CELLS Specific for Minor Histocompatibility Antigens
    Veerapathran, Anandaraman
    Beato, Francisca
    Pidala, Joseph
    Janssen, William
    Yu, Xue-Zhong
    Anasetti, Claudio
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2013, 19 (02) : S194 - S194
  • [6] MINOR HISTOCOMPATIBILITY ANTIGENS AS TARGETS FOR T-CELL IMMUNOTHERAPY
    Pilunov, A. M.
    Romaniuk, D. S.
    Efimov, G. A.
    Savchenko, V. G.
    GEMATOLOGIYA I TRANSFUZIOLOGIYA, 2021, 66 (03): : 322 - 345
  • [7] Monitoring of virus-specific T-cells with virus specific tetramers - implication for virus-specific T-cell therapy?
    Borchers, S.
    Grabow, B.
    Luther, S.
    Heuer, M.
    Ganser, A.
    Weissinger, E. M.
    BONE MARROW TRANSPLANTATION, 2007, 39 : S167 - S167
  • [8] VIRUS-SPECIFIC T-CELL SENSITIZATION - REQUIREMENTS FOR VACCINIA VIRUS-SPECIFIC T-CELL SENSITIZATION INVIVO
    ERTL, HCJ
    GERIKE, RHW
    KOSZINOWSKI, UH
    IMMUNOGENETICS, 1977, 4 (06) : 515 - 522
  • [9] Retroviral gene transfer of T cell receptors (TCR) specific for minor histocompatibility antigens to virus-specific T cells as cellular immunotherapy of patients with relapsed hematological malignancies after allogeneic stem cell transplantation.
    Griffioen, M
    van Egmond, HME
    van der Hoorn, MAG
    Hagedoorn, RS
    Kesler, M
    Falkenburg, JHF
    Heemskerk, MHM
    BLOOD, 2005, 106 (11) : 470B - 471B
  • [10] DIVERSITY OF T-CELL RECEPTORS IN VIRUS-SPECIFIC CYTOTOXIC LYMPHOCYTES-T RECOGNIZING 3 DISTINCT VIRAL EPITOPES RESTRICTED BY A SINGLE MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE
    YANAGI, Y
    TISHON, A
    LEWICKI, H
    CUBITT, BA
    OLDSTONE, MBA
    JOURNAL OF VIROLOGY, 1992, 66 (04) : 2527 - 2531