Adult and cord blood T cells can acquire HA-1 specificity through HA-1 T-cell receptor gene transfer.
OBJECTIVE
Minor histocompatibility antigen (mHag)-specific graft-versus-leukemia reactivities are observed following unselected donor lymphocyte infusion for the treatment of relapse after HLA-matched mHag-mismatched stem cell transplantation (SCT). Adoptive transfer of donor-derived ex vivo-generated HA-1-specific oligoclonal T cells or HA-1 peptide patient vaccination are currently being explored as curative tools for stem cell based immunotherapy of hematologic malignancies. Another treatment modality to eradicate residual leukemic cells after SCT is the transfer of the HA-1 hematopoietic-specific T-cell receptor (TCR) into cells from the stem cell donor. This strategy would be particularly useful in case of relapse after cord blood transplantation (CBT) and is explored in this study.


METHODS
HLA-A2(neg) adult peripheral blood and cord blood mononuclear cells were transduced with the genes encoding the HA-1 alpha and beta TCR chains derived from established HA-1 specific cytotoxic T lymphocyte clones.


RESULTS
The T cells transduced with HA-1 TCR alpha beta showed consistent marker gene expression, but low staining with HLA-A2/HA-1 tetrameric complexes. They did, however, show hematopoietic-restricted cytolytic activity against HLA-A2(pos)/HA-1(pos) target cells, including leukemic cells.


CONCLUSIONS
The low level of HA-1-specific tetramer staining of HA-1 TCR alpha beta transduced T cells may be caused by hybrid TCR formation of the transferred TCRalpha and beta chains with endogenous TCR alpha and beta chains. This may cause unwanted alloreactivity and requires attention. The HA-1 TCR alpha beta transduced T cells show that the HA-1 TCR can be functionally transferred into donor mononuclear cells, which can be exploited in immunotherapeutic settings of SCT and CBT for hematologic malignancies.
Mommaas
Bregje
B
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
van Halteren
Astrid G S
AG
Pool
Jos
J
van der Veken
Lars
L
Wieles
Brigitte
B
Heemskerk
Mirjam H M
MH
Goulmy
Els
E
D000328:Adult; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics*; D005312:Fetal Blood / Q000276:immunology*; D018014:Gene Transfer Techniques; D006801:Humans; D019169:Jurkat Cells; D015778:Minor Histocompatibility Antigens / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D009842:Oligopeptides / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage* / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; C110615:HA-1 antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell