Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion

Wandi Zhang, Jaewon Choi, Wanyong Zeng, Shelby A. Rogers, Edwin P. Alyea, James G. Rheinwald, Christine M. Canning, Vladimir Brusic, Tetsuro Sasada, Ellis L. Reinherz, Jerome Ritz, Robert J. Soiffer, Catherine J. Wu

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Abstract

Purpose: The target antigens of graft-versus-leukemia that are tumor associated are incompletely characterized. Experimental Design: We examined responses developing against CML66, an immunogenic antigen preferentially expressed in myeloid progenitor cells identified from a patient with chronic myelogenous leukemia who attained long-lived remission following CD4+ donor lymphocyte infusion (DLI). Results: From this patient, CML66-reactive CD8+ T-cell clones were detected against an endogenously presented HLA-B*4403 - restricted epitope (HDVDALLW). Neither CML66-specific antibody nor T-cell responses were detectable in peripheral blood before DLI. However, by 1 month after DLI, CD8+ T cells were present in peripheral blood and at 10-fold higher frequency in marrow. Subsequently, plasma antibody to CML66 developed in association with disease remission. Donor-derived CML66-reactive T cells were detected at low levels in vivo in marrow before DLI by ELISpot and by a nested PCR-based assay to detect clonotypic T-cell receptor sequences but not in blood of the patient pre-DLI nor of the graft donor. Conclusions: CD4+ DLI results in rapid expansion of preexisting marrow-resident leukemia-specific donor CD8+ T cells, followed by a cascade of antigen-specific immune responses detectable in blood. Our single-antigen analysis thus shows that durable posttransplant tumor immunity is directed in part against nonpolymorphic overexpressed leukemia antigens that elicit coordinated cellular and humoral immunity.

Original languageEnglish
Pages (from-to)2729-2739
Number of pages11
JournalClinical Cancer Research
Volume16
Issue number10
DOIs
Publication statusPublished - May 15 2010
Externally publishedYes

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Immunity
Leukemia
B-Lymphocytes
Tissue Donors
Lymphocytes
T-Lymphocytes
Transplants
Antigens
Bone Marrow
Myeloid Progenitor Cells
HLA-B Antigens
Antibodies
Histocompatibility Antigens Class II
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Humoral Immunity
T-Cell Antigen Receptor
Blood Donors
Cellular Immunity
Epitopes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zhang, W., Choi, J., Zeng, W., Rogers, S. A., Alyea, E. P., Rheinwald, J. G., ... Wu, C. J. (2010). Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion. Clinical Cancer Research, 16(10), 2729-2739. https://doi.org/10.1158/1078-0432.CCR-10-0415

Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion. / Zhang, Wandi; Choi, Jaewon; Zeng, Wanyong; Rogers, Shelby A.; Alyea, Edwin P.; Rheinwald, James G.; Canning, Christine M.; Brusic, Vladimir; Sasada, Tetsuro; Reinherz, Ellis L.; Ritz, Jerome; Soiffer, Robert J.; Wu, Catherine J.

In: Clinical Cancer Research, Vol. 16, No. 10, 15.05.2010, p. 2729-2739.

Research output: Contribution to journalArticle

Zhang, W, Choi, J, Zeng, W, Rogers, SA, Alyea, EP, Rheinwald, JG, Canning, CM, Brusic, V, Sasada, T, Reinherz, EL, Ritz, J, Soiffer, RJ & Wu, CJ 2010, 'Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion', Clinical Cancer Research, vol. 16, no. 10, pp. 2729-2739. https://doi.org/10.1158/1078-0432.CCR-10-0415
Zhang, Wandi ; Choi, Jaewon ; Zeng, Wanyong ; Rogers, Shelby A. ; Alyea, Edwin P. ; Rheinwald, James G. ; Canning, Christine M. ; Brusic, Vladimir ; Sasada, Tetsuro ; Reinherz, Ellis L. ; Ritz, Jerome ; Soiffer, Robert J. ; Wu, Catherine J. / Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 10. pp. 2729-2739.
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abstract = "Purpose: The target antigens of graft-versus-leukemia that are tumor associated are incompletely characterized. Experimental Design: We examined responses developing against CML66, an immunogenic antigen preferentially expressed in myeloid progenitor cells identified from a patient with chronic myelogenous leukemia who attained long-lived remission following CD4+ donor lymphocyte infusion (DLI). Results: From this patient, CML66-reactive CD8+ T-cell clones were detected against an endogenously presented HLA-B*4403 - restricted epitope (HDVDALLW). Neither CML66-specific antibody nor T-cell responses were detectable in peripheral blood before DLI. However, by 1 month after DLI, CD8+ T cells were present in peripheral blood and at 10-fold higher frequency in marrow. Subsequently, plasma antibody to CML66 developed in association with disease remission. Donor-derived CML66-reactive T cells were detected at low levels in vivo in marrow before DLI by ELISpot and by a nested PCR-based assay to detect clonotypic T-cell receptor sequences but not in blood of the patient pre-DLI nor of the graft donor. Conclusions: CD4+ DLI results in rapid expansion of preexisting marrow-resident leukemia-specific donor CD8+ T cells, followed by a cascade of antigen-specific immune responses detectable in blood. Our single-antigen analysis thus shows that durable posttransplant tumor immunity is directed in part against nonpolymorphic overexpressed leukemia antigens that elicit coordinated cellular and humoral immunity.",
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AU - Zhang, Wandi

AU - Choi, Jaewon

AU - Zeng, Wanyong

AU - Rogers, Shelby A.

AU - Alyea, Edwin P.

AU - Rheinwald, James G.

AU - Canning, Christine M.

AU - Brusic, Vladimir

AU - Sasada, Tetsuro

AU - Reinherz, Ellis L.

AU - Ritz, Jerome

AU - Soiffer, Robert J.

AU - Wu, Catherine J.

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N2 - Purpose: The target antigens of graft-versus-leukemia that are tumor associated are incompletely characterized. Experimental Design: We examined responses developing against CML66, an immunogenic antigen preferentially expressed in myeloid progenitor cells identified from a patient with chronic myelogenous leukemia who attained long-lived remission following CD4+ donor lymphocyte infusion (DLI). Results: From this patient, CML66-reactive CD8+ T-cell clones were detected against an endogenously presented HLA-B*4403 - restricted epitope (HDVDALLW). Neither CML66-specific antibody nor T-cell responses were detectable in peripheral blood before DLI. However, by 1 month after DLI, CD8+ T cells were present in peripheral blood and at 10-fold higher frequency in marrow. Subsequently, plasma antibody to CML66 developed in association with disease remission. Donor-derived CML66-reactive T cells were detected at low levels in vivo in marrow before DLI by ELISpot and by a nested PCR-based assay to detect clonotypic T-cell receptor sequences but not in blood of the patient pre-DLI nor of the graft donor. Conclusions: CD4+ DLI results in rapid expansion of preexisting marrow-resident leukemia-specific donor CD8+ T cells, followed by a cascade of antigen-specific immune responses detectable in blood. Our single-antigen analysis thus shows that durable posttransplant tumor immunity is directed in part against nonpolymorphic overexpressed leukemia antigens that elicit coordinated cellular and humoral immunity.

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