Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens

Edus H. Warren, Nobuharu Fujii, Yoshiki Akatsuka, Colette N. Chaney, Jeffrey K. Mito, Keith R. Loeb, Ted A. Gooley, Michele L. Brown, Kevin K.W. Koo, Kellie V. Rosinski, Seishi Ogawa, Aiko Matsubara, Frederick R. Appelbaum, Stanley R. Riddell

Research output: Contribution to journalArticle

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Abstract

The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)-matched allogeneic HCT were treated with infusions of donor-derived, ex vivo-expanded CD8+ cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.

Original languageEnglish
Pages (from-to)3869-3878
Number of pages10
JournalBlood
Volume115
Issue number19
DOIs
Publication statusPublished - 13-05-2010

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Minor Histocompatibility Antigens
T-cells
Cell Transplantation
Leukemia
T-Lymphocytes
Cytotoxic T-Lymphocytes
Adoptive Transfer
Clone Cells
Cell- and Tissue-Based Therapy
Tissue Donors
Therapeutics
Safety
Lung
Major Histocompatibility Complex
Tissue
Gene encoding
Grafts
Transplants
Recurrence
Toxicity

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Warren, E. H., Fujii, N., Akatsuka, Y., Chaney, C. N., Mito, J. K., Loeb, K. R., ... Riddell, S. R. (2010). Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. Blood, 115(19), 3869-3878. https://doi.org/10.1182/blood-2009-10-248997
Warren, Edus H. ; Fujii, Nobuharu ; Akatsuka, Yoshiki ; Chaney, Colette N. ; Mito, Jeffrey K. ; Loeb, Keith R. ; Gooley, Ted A. ; Brown, Michele L. ; Koo, Kevin K.W. ; Rosinski, Kellie V. ; Ogawa, Seishi ; Matsubara, Aiko ; Appelbaum, Frederick R. ; Riddell, Stanley R. / Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. In: Blood. 2010 ; Vol. 115, No. 19. pp. 3869-3878.
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abstract = "The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)-matched allogeneic HCT were treated with infusions of donor-derived, ex vivo-expanded CD8+ cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.",
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Warren, EH, Fujii, N, Akatsuka, Y, Chaney, CN, Mito, JK, Loeb, KR, Gooley, TA, Brown, ML, Koo, KKW, Rosinski, KV, Ogawa, S, Matsubara, A, Appelbaum, FR & Riddell, SR 2010, 'Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens', Blood, vol. 115, no. 19, pp. 3869-3878. https://doi.org/10.1182/blood-2009-10-248997

Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. / Warren, Edus H.; Fujii, Nobuharu; Akatsuka, Yoshiki; Chaney, Colette N.; Mito, Jeffrey K.; Loeb, Keith R.; Gooley, Ted A.; Brown, Michele L.; Koo, Kevin K.W.; Rosinski, Kellie V.; Ogawa, Seishi; Matsubara, Aiko; Appelbaum, Frederick R.; Riddell, Stanley R.

In: Blood, Vol. 115, No. 19, 13.05.2010, p. 3869-3878.

Research output: Contribution to journalArticle

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T1 - Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens

AU - Warren, Edus H.

AU - Fujii, Nobuharu

AU - Akatsuka, Yoshiki

AU - Chaney, Colette N.

AU - Mito, Jeffrey K.

AU - Loeb, Keith R.

AU - Gooley, Ted A.

AU - Brown, Michele L.

AU - Koo, Kevin K.W.

AU - Rosinski, Kellie V.

AU - Ogawa, Seishi

AU - Matsubara, Aiko

AU - Appelbaum, Frederick R.

AU - Riddell, Stanley R.

PY - 2010/5/13

Y1 - 2010/5/13

N2 - The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)-matched allogeneic HCT were treated with infusions of donor-derived, ex vivo-expanded CD8+ cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.

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