Elimination of the chemotherapy resistant subpopulation of 4T1 XXXX @entity0 by haploidentical NK cells cures the vast majority of @entity19 .

@entity1 @entity632 @entity0 @entity19 @entity5 @entity900 @entity786
Metastatic @entity0 is currently incurable despite initial responsiveness, assumingly due to the presence of chemoresistant subpopulations that can be characterized as label retaining cells (LRC). In the 4T1 @entity19 @entity0 model, we previously achieved cure after @entity786 and Total Body Irradiation (CY + TBI) followed by haploidentical bone marrow and spleen transplantation (BMSPLT). CY + TBI without transplantation induced only transient @entity5 growth indicating a critical role of donor immune cells. As it remained unknown if the 4T1 model resembles @entity1 disease with respect to the presence of subpopulations of chemoresistant LRC, we now demonstrate this is indeed the case. Chemoresistance of 4T1 LRC was demonstrated by in vitro co-incubation of fluorescently labeled 4T1 cells in limiting dilution with @entity786 , @entity632 or @entity900 , after which only LRC containing colonies remained. LRC also remain in vivo after treatment with CY + TBI. Succeeding experiments set up to identify the haploidentical effector cell responsible for cure and, therefore, for the elimination of chemoresistant LRC designate donor NK cells crucial for the anti- @entity5 effect. NK cell depletion of the haploidentical graft fully abrogated the anti- @entity5 effect. Increased disease-free survival retained after transplantation of haploidentical bone marrow and NK cell-enriched spleen cell grafts, even in the absence of donor T-cells or of donor bone marrow. Tumor growth analysis indicates the anti- @entity5 effect being immediate (days). Based on these data, it is worthwhile to explore alloreactive adoptive NK cell therapy as consolidation for @entity1 with metastasized @entity0 .
