Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion

Enrica Orsini, Roberto Bellucci, Edwin P. Alyea, Robert Schlossman, Christine Canning, Stephen McLaughlin, Paolo Ghia, Kenneth C. Anderson, Jerome Ritz

Research output: Contribution to journalArticle

Abstract

Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been identified. Molecular analysis of CDR3 Vβ repertoire after CD4+ DLI demonstrated previously that the development of GVM and graft-versus-host-disease (GVHD) were associated with the clonal expansion of distinct T-cell populations in patient peripheral blood. In the current study, we undertook a molecular and functional characterization of GVM- and GVHD-associated T-cell clones. T-cell clones associated with GVM were detectable by clone-specific PCR at a low level in peripheral blood before DLI and expanded ∼10-fold after DLI. In contrast, T-cell clones associated with GVHD were not detectable before DLI or before the development of clinical GVHD. Two T-cell clones associated with GVM were isolated and expanded in vitro, allowing their phenotypic and functional characterization. Both GVM clones were derived from donor cells and had a CD3+CD8+CD4- phenotype. One GVM clone specifically recognized patient myeloma cells in an HLA class I-restricted manner, but was not reactive with patient normal bone marrow cells or patient EBV transformed B cells. Taken together, these findings suggest that the GVM response is mediated by donor-derived CD8+ T-cell clones with antimyeloma specificity that may be present before DLI. In contrast, T-cell clones associated with GVHD are expanded de novo after DLI.

Original languageEnglish
Pages (from-to)2561-2568
Number of pages8
JournalCancer Research
Volume63
Issue number10
Publication statusPublished - May 15 2003

Fingerprint

Clone Cells
Tissue Donors
Lymphocytes
T-Lymphocytes
Graft vs Host Disease
Transplants
Neoplasms
Homologous Transplantation
Blood Donors
Multiple Myeloma
Bone Marrow Transplantation
Human Herpesvirus 4
Bone Marrow Cells
B-Lymphocytes
Phenotype
Antigens
Polymerase Chain Reaction
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Orsini, E., Bellucci, R., Alyea, E. P., Schlossman, R., Canning, C., McLaughlin, S., ... Ritz, J. (2003). Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion. Cancer Research, 63(10), 2561-2568.

Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion. / Orsini, Enrica; Bellucci, Roberto; Alyea, Edwin P.; Schlossman, Robert; Canning, Christine; McLaughlin, Stephen; Ghia, Paolo; Anderson, Kenneth C.; Ritz, Jerome.

In: Cancer Research, Vol. 63, No. 10, 15.05.2003, p. 2561-2568.

Research output: Contribution to journalArticle

Orsini, E, Bellucci, R, Alyea, EP, Schlossman, R, Canning, C, McLaughlin, S, Ghia, P, Anderson, KC & Ritz, J 2003, 'Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion', Cancer Research, vol. 63, no. 10, pp. 2561-2568.
Orsini E, Bellucci R, Alyea EP, Schlossman R, Canning C, McLaughlin S et al. Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion. Cancer Research. 2003 May 15;63(10):2561-2568.
Orsini, Enrica ; Bellucci, Roberto ; Alyea, Edwin P. ; Schlossman, Robert ; Canning, Christine ; McLaughlin, Stephen ; Ghia, Paolo ; Anderson, Kenneth C. ; Ritz, Jerome. / Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion. In: Cancer Research. 2003 ; Vol. 63, No. 10. pp. 2561-2568.
@article{edd4b3a037204fc7b274923a92a00ed2,
title = "Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion",
abstract = "Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been identified. Molecular analysis of CDR3 Vβ repertoire after CD4+ DLI demonstrated previously that the development of GVM and graft-versus-host-disease (GVHD) were associated with the clonal expansion of distinct T-cell populations in patient peripheral blood. In the current study, we undertook a molecular and functional characterization of GVM- and GVHD-associated T-cell clones. T-cell clones associated with GVM were detectable by clone-specific PCR at a low level in peripheral blood before DLI and expanded ∼10-fold after DLI. In contrast, T-cell clones associated with GVHD were not detectable before DLI or before the development of clinical GVHD. Two T-cell clones associated with GVM were isolated and expanded in vitro, allowing their phenotypic and functional characterization. Both GVM clones were derived from donor cells and had a CD3+CD8+CD4- phenotype. One GVM clone specifically recognized patient myeloma cells in an HLA class I-restricted manner, but was not reactive with patient normal bone marrow cells or patient EBV transformed B cells. Taken together, these findings suggest that the GVM response is mediated by donor-derived CD8+ T-cell clones with antimyeloma specificity that may be present before DLI. In contrast, T-cell clones associated with GVHD are expanded de novo after DLI.",
author = "Enrica Orsini and Roberto Bellucci and Alyea, {Edwin P.} and Robert Schlossman and Christine Canning and Stephen McLaughlin and Paolo Ghia and Anderson, {Kenneth C.} and Jerome Ritz",
year = "2003",
month = "5",
day = "15",
language = "English",
volume = "63",
pages = "2561--2568",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion

AU - Orsini, Enrica

AU - Bellucci, Roberto

AU - Alyea, Edwin P.

AU - Schlossman, Robert

AU - Canning, Christine

AU - McLaughlin, Stephen

AU - Ghia, Paolo

AU - Anderson, Kenneth C.

AU - Ritz, Jerome

PY - 2003/5/15

Y1 - 2003/5/15

N2 - Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been identified. Molecular analysis of CDR3 Vβ repertoire after CD4+ DLI demonstrated previously that the development of GVM and graft-versus-host-disease (GVHD) were associated with the clonal expansion of distinct T-cell populations in patient peripheral blood. In the current study, we undertook a molecular and functional characterization of GVM- and GVHD-associated T-cell clones. T-cell clones associated with GVM were detectable by clone-specific PCR at a low level in peripheral blood before DLI and expanded ∼10-fold after DLI. In contrast, T-cell clones associated with GVHD were not detectable before DLI or before the development of clinical GVHD. Two T-cell clones associated with GVM were isolated and expanded in vitro, allowing their phenotypic and functional characterization. Both GVM clones were derived from donor cells and had a CD3+CD8+CD4- phenotype. One GVM clone specifically recognized patient myeloma cells in an HLA class I-restricted manner, but was not reactive with patient normal bone marrow cells or patient EBV transformed B cells. Taken together, these findings suggest that the GVM response is mediated by donor-derived CD8+ T-cell clones with antimyeloma specificity that may be present before DLI. In contrast, T-cell clones associated with GVHD are expanded de novo after DLI.

AB - Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been identified. Molecular analysis of CDR3 Vβ repertoire after CD4+ DLI demonstrated previously that the development of GVM and graft-versus-host-disease (GVHD) were associated with the clonal expansion of distinct T-cell populations in patient peripheral blood. In the current study, we undertook a molecular and functional characterization of GVM- and GVHD-associated T-cell clones. T-cell clones associated with GVM were detectable by clone-specific PCR at a low level in peripheral blood before DLI and expanded ∼10-fold after DLI. In contrast, T-cell clones associated with GVHD were not detectable before DLI or before the development of clinical GVHD. Two T-cell clones associated with GVM were isolated and expanded in vitro, allowing their phenotypic and functional characterization. Both GVM clones were derived from donor cells and had a CD3+CD8+CD4- phenotype. One GVM clone specifically recognized patient myeloma cells in an HLA class I-restricted manner, but was not reactive with patient normal bone marrow cells or patient EBV transformed B cells. Taken together, these findings suggest that the GVM response is mediated by donor-derived CD8+ T-cell clones with antimyeloma specificity that may be present before DLI. In contrast, T-cell clones associated with GVHD are expanded de novo after DLI.

UR - http://www.scopus.com/inward/record.url?scp=0037505840&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037505840&partnerID=8YFLogxK

M3 - Article

C2 - 12750280

AN - SCOPUS:0037505840

VL - 63

SP - 2561

EP - 2568

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 10

ER -