Originally published as JCO Early Release 10.1200/JCO.2004.01.127 on August 16 2004

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Allogeneic Lymphocytes Induce Tumor Regression of Advanced Metastatic Breast Cancer

From the Experimental Transplantation and Immunology Branch and Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Diagnostic Radiology Department and Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD.

Address reprint requests to Michael R. Bishop, MD, Experimental Transplantation and Immunology Branch, Center for Cancer Research/National Cancer Institute/National Institutes of Health, Building 10, Room 12N226, Bethesda, MD 20892; e-mail: mbishop{at}mail.nih.gov

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 x 10⁶, 5 x 10⁶, and 10 x 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.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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