Novel strategies to target cancer stem cells by NK cells; studies in humanized mice.
We have previously shown that following selection, Natural Killer (NK) cells, differentiate Cancer stem cells (CSCs)/undifferentiated or poorly differentiated tumors via secreted and membrane bound IFN-gamma and TNF-alpha, leading to prevention of tumor growth and remodeling of the tumor microenvironment. Since conventional therapeutic strategies including chemotherapy and radiotherapy remain unsuccessful in treating stem-like tumors, there has been an increasing interest in NK cell based immunotherapy for the treatment of resistant tumors. In our recent studies, we used bone marrow, liver, thymus humanized (hu-BLT) mouse model to demonstrate the efficacy of adoptive transfer ofex vivoexpanded super-charged NK cells in the selection and differentiation of stem-like tumors within the context of a fully reconstituted human immune system. We have also shown that CSCs differentiated with split anergized NK cells prior to implantation in humanized mice did not grow or metastasize. In this review, we present current advances in NK cell detection, expansion and therapeutic delivery, and discuss the utility of different humanized mouse models in studying NK cell based therapies in the preclinical settings.
Division of Oral Biology and Oral Medicine, Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles,CA,USA and Department of Tumor Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Polan.
Anna K
AK
Kozlowska
Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA.
Kawaljit
K
Kaur
Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA.
Paytsar
P
Topchyan
Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA, Los Angeles, CA, USA, The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA, USA, ajewett@ucla.edu.
Anahid
A
Jewett
D000818:Animals; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation; D064593:Heterografts; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology*; D059016:Tumor Microenvironment / Q000276:immunology