Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer

Michael R. Bishop, Daniel H. Fowler, Donna Marchigiani, Kathleen Castro, Claude Sportes, Seth M. Steinberg, Juan C. Gea-Banacloche, Robert Dean, Catherine K. Chow, Charles Carter, Elizabeth J. Read, Susan Leitman, Ronald Gress

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Abstract

Purpose: Allogeneic T lymphocytes can induce regression of metastatic breast cancer through an immune-mediated graft-versus-tumor (GVT) effect in murine models. To determine if a clinical GVT effect exists against metastatic breast cancer, allogeneic lymphocytes were used as adoptive cellular therapy after a reduced-intensity chemotherapy conditioning regimen and allogeneic hematopoietic stem-cell transplantation (HSCT) from human leukocyte antigen-matched siblings. Patients and Methods: Sixteen patients with metastatic breast cancer that had progressed after treatment with anthracyclines, taxanes, hormonal agents, and trastuzumab, received allogeneic HSCT. The reduced-intensity transplant conditioning regimen consisted of cyclophosphamide and fludarabine. To distinguish an immunological GVT effect from any antitumor effect of cytotoxic chemotherapy in the transplant-conditioning regimen, allogeneic T lymphocytes were removed from the stem-cell graft and were subsequently administered late postallogeneic HSCT. Allogeneic lymphocytes containing 1 × 106, 5 × 106, and 10 × 106 CD3+ cells/kg were infused on days +42, +70, and +98 post-allogeneic HSCT, respectively. Results: Objective tumor regressions occurred after day +28 post-allogeneic HSCT in six patients and were attributed to allogeneic lymphocyte infusions. Two of these responding patients had disease progression post-allogeneic HSCT before subsequent tumor regression. Tumor regressions occurred concomitantly with the establishment of complete donor T-lymphoid engraftment, were associated with the development of graft-versus-host disease (GVHD), and were abrogated by subsequent systemic immunosuppression for GVHD. Conclusion: Allogeneic lymphocytes can induce regression of advanced metastatic breast cancer. These results indicate that an immunological GVT effect from allogeneic lymphocytes exists against metastatic breast cancer and provide rationale for further development of allogeneic cellular therapy for this largely incurable disease.

Original languageEnglish (US)
Pages (from-to)3886-3892
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number19
DOIs
StatePublished - Dec 1 2004

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Hematopoietic Stem Cell Transplantation
Lymphocytes
Breast Neoplasms
Transplants
Neoplasms
Graft vs Host Disease
T-Lymphocytes
Drug Therapy
Taxoids
Anthracyclines
HLA Antigens
Cyclophosphamide
Immunosuppression
Disease Progression
Siblings
Stem Cells
Therapeutics
Tissue Donors
Conditioning (Psychology)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Bishop, M. R., Fowler, D. H., Marchigiani, D., Castro, K., Sportes, C., Steinberg, S. M., ... Gress, R. (2004). Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer. Journal of Clinical Oncology, 22(19), 3886-3892. https://doi.org/10.1200/JCO.2004.01.127

Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer. / Bishop, Michael R.; Fowler, Daniel H.; Marchigiani, Donna; Castro, Kathleen; Sportes, Claude; Steinberg, Seth M.; Gea-Banacloche, Juan C.; Dean, Robert; Chow, Catherine K.; Carter, Charles; Read, Elizabeth J.; Leitman, Susan; Gress, Ronald.

In: Journal of Clinical Oncology, Vol. 22, No. 19, 01.12.2004, p. 3886-3892.

Research output: Contribution to journalArticle

Bishop, MR, Fowler, DH, Marchigiani, D, Castro, K, Sportes, C, Steinberg, SM, Gea-Banacloche, JC, Dean, R, Chow, CK, Carter, C, Read, EJ, Leitman, S & Gress, R 2004, 'Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer', Journal of Clinical Oncology, vol. 22, no. 19, pp. 3886-3892. https://doi.org/10.1200/JCO.2004.01.127
Bishop MR, Fowler DH, Marchigiani D, Castro K, Sportes C, Steinberg SM et al. Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer. Journal of Clinical Oncology. 2004 Dec 1;22(19):3886-3892. https://doi.org/10.1200/JCO.2004.01.127
Bishop, Michael R. ; Fowler, Daniel H. ; Marchigiani, Donna ; Castro, Kathleen ; Sportes, Claude ; Steinberg, Seth M. ; Gea-Banacloche, Juan C. ; Dean, Robert ; Chow, Catherine K. ; Carter, Charles ; Read, Elizabeth J. ; Leitman, Susan ; Gress, Ronald. / Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 19. pp. 3886-3892.
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abstract = "Purpose: Allogeneic T lymphocytes can induce regression of metastatic breast cancer through an immune-mediated graft-versus-tumor (GVT) effect in murine models. To determine if a clinical GVT effect exists against metastatic breast cancer, allogeneic lymphocytes were used as adoptive cellular therapy after a reduced-intensity chemotherapy conditioning regimen and allogeneic hematopoietic stem-cell transplantation (HSCT) from human leukocyte antigen-matched siblings. Patients and Methods: Sixteen patients with metastatic breast cancer that had progressed after treatment with anthracyclines, taxanes, hormonal agents, and trastuzumab, received allogeneic HSCT. The reduced-intensity transplant conditioning regimen consisted of cyclophosphamide and fludarabine. To distinguish an immunological GVT effect from any antitumor effect of cytotoxic chemotherapy in the transplant-conditioning regimen, allogeneic T lymphocytes were removed from the stem-cell graft and were subsequently administered late postallogeneic HSCT. Allogeneic lymphocytes containing 1 × 106, 5 × 106, and 10 × 106 CD3+ cells/kg were infused on days +42, +70, and +98 post-allogeneic HSCT, respectively. Results: Objective tumor regressions occurred after day +28 post-allogeneic HSCT in six patients and were attributed to allogeneic lymphocyte infusions. Two of these responding patients had disease progression post-allogeneic HSCT before subsequent tumor regression. Tumor regressions occurred concomitantly with the establishment of complete donor T-lymphoid engraftment, were associated with the development of graft-versus-host disease (GVHD), and were abrogated by subsequent systemic immunosuppression for GVHD. Conclusion: Allogeneic lymphocytes can induce regression of advanced metastatic breast cancer. These results indicate that an immunological GVT effect from allogeneic lymphocytes exists against metastatic breast cancer and provide rationale for further development of allogeneic cellular therapy for this largely incurable disease.",
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AU - Gea-Banacloche, Juan C.

AU - Dean, Robert

AU - Chow, Catherine K.

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AU - Read, Elizabeth J.

AU - Leitman, Susan

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N2 - Purpose: Allogeneic T lymphocytes can induce regression of metastatic breast cancer through an immune-mediated graft-versus-tumor (GVT) effect in murine models. To determine if a clinical GVT effect exists against metastatic breast cancer, allogeneic lymphocytes were used as adoptive cellular therapy after a reduced-intensity chemotherapy conditioning regimen and allogeneic hematopoietic stem-cell transplantation (HSCT) from human leukocyte antigen-matched siblings. Patients and Methods: Sixteen patients with metastatic breast cancer that had progressed after treatment with anthracyclines, taxanes, hormonal agents, and trastuzumab, received allogeneic HSCT. The reduced-intensity transplant conditioning regimen consisted of cyclophosphamide and fludarabine. To distinguish an immunological GVT effect from any antitumor effect of cytotoxic chemotherapy in the transplant-conditioning regimen, allogeneic T lymphocytes were removed from the stem-cell graft and were subsequently administered late postallogeneic HSCT. Allogeneic lymphocytes containing 1 × 106, 5 × 106, and 10 × 106 CD3+ cells/kg were infused on days +42, +70, and +98 post-allogeneic HSCT, respectively. Results: Objective tumor regressions occurred after day +28 post-allogeneic HSCT in six patients and were attributed to allogeneic lymphocyte infusions. Two of these responding patients had disease progression post-allogeneic HSCT before subsequent tumor regression. Tumor regressions occurred concomitantly with the establishment of complete donor T-lymphoid engraftment, were associated with the development of graft-versus-host disease (GVHD), and were abrogated by subsequent systemic immunosuppression for GVHD. Conclusion: Allogeneic lymphocytes can induce regression of advanced metastatic breast cancer. These results indicate that an immunological GVT effect from allogeneic lymphocytes exists against metastatic breast cancer and provide rationale for further development of allogeneic cellular therapy for this largely incurable disease.

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