Induction of Minor Histocompatibility Antigen HA-1–Specific Cytotoxic T Cells for the Treatment of Leukemia After Allogeneic Stem Cell Transplantation

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4374-4376 ◽  
Author(s):  
Peter Brossart ◽  
Brigitte Spahlinger ◽  
Frank Grünebach ◽  
Gernot Stuhler ◽  
Volker L. Reichardt ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cytotoxic T Cells ◽  
Histocompatibility Antigen ◽  
Minor Histocompatibility Antigen

scholarly journals Off-the-shelf TCR for graft-versus-leukemia without GVHD

Blood ◽  
2018 ◽  
Vol 131 (1) ◽  
pp. 5-7
Author(s):  
Frederick L. Locke ◽  
Claudio Anasetti
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
T Cell Receptor ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Receptor ◽  
Histocompatibility Antigen ◽  
Minor Histocompatibility Antigen ◽  
Graft Versus Leukemia ◽  
Leukemia Relapse

In this issue of Blood, Dossa et al report the engineering of T-cell receptor (TCR) transgenic T cells against the human minor histocompatibility antigen HA-1 for the prevention or treatment of leukemia relapse after allogeneic stem cell transplantation.1

Generation of minor histocompatibility antigen HA-1–specific cytotoxic T cells restricted by nonself HLA molecules: a potential strategy to treat relapsed leukemia after HLA-mismatched stem cell transplantation

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 547-552 ◽  
Author(s):  
Tuna Mutis ◽  
Els Blokland ◽  
Michel Kester ◽  
Ellen Schrama ◽  
Els Goulmy
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cytotoxic T Cells ◽  
Histocompatibility Antigen ◽  
Minor Histocompatibility Antigen ◽  
Hematopoietic System ◽  
Specific Ctls ◽  
Potential Strategy ◽  
Hla Molecules

Abstract Successful stem cell transplantation (SCT) across HLA barriers can be performed with cord blood, megadoses of stem cells, or with nonmyeloablative conditioning strategies. Because the HLA-mismatched transplants are often T-cell depleted, leukemia relapse rates are high. Treatment of relapsed leukemia after HLA-mismatched SCT is difficult. A novel potential strategy to treat relapsed leukemia after HLA-mismatched SCT is the use of patients' mismatched HLA molecules as antigen-presenting molecules to generate hematopoietic system–specific cytotoxic T cells (CTLs) from the stem cell donor. Adoptive transfer of these hematopoietic system–specific CTLs that are restricted by nonself HLA molecules may eliminate leukemia without affecting the patient's nonhematopoietic cells or donor hematopoietic cells. We investigated the feasibility of this strategy using the hematopoietic system–specific minor histocompatibility antigen HA-1, which is known to induce HLA-A2–restricted CTLs. HLA-A2−peripheral blood mononuclear cells were stimulated with HLA-A2+ T2 cells pulsed with synthetic HA-1 peptide or with dendritic cells transduced with the HA-1 cDNA. Tetrameric HLA-A2/HA-1 peptide complexes were used to monitor and enrich HA-1–specific CTLs. In the alloreactive cultures, HA-1–specific CTLs were enriched up to 7% by 3 rounds of antigen-specific stimulations and up to 87% by fluorescence-activated cell sorting of tetramer-positive T cells. The HA-1–specific CTLs showed specific lysis of the relevant target cells, including leukemic cells. Because the polyclonal CTL cultures also contained natural killer cells and allo–HLA-A2–specific CTLs, CTL clones were generated that showed the expected HA-1 specificity only. Thus, HA-1–specific CTLs restricted by nonself HLA-A2 molecules can be generated in an HLA-A2–mismatched setting.

Pregnancy induces minor histocompatibility antigen–specific cytotoxic T cells: implications for stem cell transplantation and immunotherapy

Blood ◽  
2004 ◽  
Vol 103 (5) ◽  
pp. 1961-1964 ◽  
Author(s):  
Rob M. Verdijk ◽  
Antoinette Kloosterman ◽  
Jos Pool ◽  
Maarten van de Keur ◽  
Albert M. I. H. Naipal ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Mononuclear Cells ◽  
Cytotoxic T Cells ◽  
Minor Histocompatibility Antigen ◽  
Peripheral Blood Mononuclear ◽  
Cell Transplants ◽  
Multiparous Female

AbstractRecipients of HLA-identical stem cell transplants have a poorer transplant outcome if the donor is female rather than male. We analyzed whether pregnancy primes for minor histocompatibility (H) antigens. Peripheral blood mononuclear cells (PBMCs) from healthy multiparous female blood donors were depleted for CD4+, CD14+, CD16+, and CD19+ cells, stained with minor H antigen–specific HLA-A2 tetramers, sorted by fluorescence-activated cell sorting, and tested for cytotoxic activity. Minor H antigens HY-, HA-1–, and HA-2–specific cytotoxic T cells (CD8+, CD45RA–) were present in PBMCs from 4 of 7 female donors up to 22 years after the last delivery. Interestingly, in 2 of the 4 cases microchimerism of the putative immunizing minor H antigen was observed. Thus, pregnancy can lead to alloimmune responses against the infant's paternal minor H antigens. The minor H antigen immunization status of female donors raises important questions for the clinical practice of stem cell transplantation.

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