Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer.
OBJECTIVE
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.


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 10(6), 5 x 10(6), and 10 x 10(6) 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.


CONCLUSIONS
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.
Experimental Transplantation and Immunology Branch, Center for Cancer Research/National Cancer Institute/National Institutes of Health, Building 10, Room 12N226, Bethesda, MD 20892, USA. mbishop@mail.nih.gov
Michael R
MR
Bishop
Daniel H
DH
Fowler
Donna
D
Marchigiani
Kathleen
K
Castro
Claude
C
Kasten-Sportes
Seth M
SM
Steinberg
Juan C
JC
Gea-Banacloche
Robert
R
Dean
Catherine K
CK
Chow
Charles
C
Carter
Elizabeth J
EJ
Read
Susan
S
Leitman
Ronald
R
Gress
D019264:Adoptive Transfer / Q000379:methods*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous