Graft-versus-tumor effects on murine mammary carcinoma in a model of nonmyeloablative haploidentical stem cell transplantation.
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.
Vanclée
A
A
Department of Internal Medicine, Division of Hematology and Oncology, University Hospital Maastricht, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands. a.vanclee@immuno.unimaas.nl
van Gelder
M
M
Schouten
H C
HC
Bos
G M J
GM
D000818:Animals; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology; D006086:Graft vs Host Disease / Q000517:prevention & control; D020350:Graft vs Tumor Effect; D006239:Haplotypes; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000628:therapy*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7