TY - JOUR
T1 - Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer
AU - Bishop, Michael R.
AU - Fowler, Daniel H.
AU - Marchigiani, Donna
AU - Castro, Kathleen
AU - Kasten-Sportes, Claude
AU - Steinberg, Seth M.
AU - Gea-Banacloche, Juan C.
AU - Dean, Robert
AU - Chow, Catherine K.
AU - Carter, Charles
AU - Read, Elizabeth J.
AU - Leitman, Susan
AU - Gress, Ronald
PY - 2004
Y1 - 2004
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=4644245960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4644245960&partnerID=8YFLogxK
U2 - 10.1200/JCO.2004.01.127
DO - 10.1200/JCO.2004.01.127
M3 - Article
C2 - 15314059
AN - SCOPUS:4644245960
SN - 0732-183X
VL - 22
SP - 3886
EP - 3892
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 19
ER -