Graft-versus-tumor effects on murine mammary carcinoma in a model of nonmyeloablative haploidentical stem cell transplantation

• Published in: Bone marrow transplantation (Basingstoke) Vol. 37; no. 11; pp. 1043 - 1049
• Main Authors: VANCLEE, A, VAN GELDER, M, SCHOUTEN, H. C, BOS, G. M. J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.2006
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anticancer properties; Biological and medical sciences; Bone marrow; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Bone tumors; Breast cancer; Carcinoma; Care and treatment; Complications and side effects; Diagnosis; Female; Fibroblast Growth Factor 7 - pharmacology; Graft versus host disease; Graft versus host reaction; Graft vs Host Disease - prevention & control; Graft vs Tumor Effect; Grafting; Growth factors; Gynecology. Andrology. Obstetrics; Haplotypes; Health services; Humans; Keratinocyte growth factor; Male; Mammary gland; Mammary gland diseases; Mammary Neoplasms, Experimental - therapy; Medical sciences; Mice; Mortality; Prophylaxis; Recombinant Proteins - pharmacology; Risk factors; Splenocytes; Stem Cell Transplantation; Stem cells; Syngeneic grafts; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning; Transplantation, Homologous; Transplantation, Isogeneic; Tumors; Netherlands; Animal model; Hematology; Graft versus tumor reaction; nonmyeloablative; Stem cell; stem cell transplantation; Rodentia; Hematopoietic cell; Breast cancer; Non myeloablative treatment; Keratinocyte growth factor; Malignant tumor; haploidentical; Breast carcinoma; Mammary gland diseases; Vertebrata; Mammalia; Mouse; Graft
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1705383

Despite a slight decrease in mortality over the last decade, breast cancer still remains a leading cause of cancer-related death in women. Although anti-tumor effects have been observed after allogeneic stem cell transplantation (SCT), this treatment is not standard care owing to graft-versus-host disease (GVHD) and scarcity of suitable donors. With the aim of reducing treatment-related mortality and increasing donor availability in clinical situations, we developed a preclinical mouse model that combines nonmyeloablative conditioning with the use of haploidentical donor-recipient pairs. To mimic active disease, CB6F1 mice were inoculated with 5 x 10(4) 4T1 mammary carcinoma cells 10 days before transplantation. Keratinocyte growth factor (KGF) was used as GVHD prophylaxis. Syngeneic (CB6F1) SCT did not cure any of the mice and KGF treatment did not influence tumor development. After transplantation with haploidentical (B6CBAF1) bone marrow and splenocytes, however, tumor outgrowth was reduced and long-term disease-free survival (>3 months) was observed in 9/18 (50%) (P=0.0011) of the animals. We conclude that in a model of murine breast cancer, a graft-versus-tumor effect can be induced by a nonmyeloablative haploidentical SCT procedure.