title: Toward a stem cell gene therapy for breast cancer.
abstract: Current approaches for treatment of late-stage breast cancer rarely result in a long-term cure. In part this is due to tumor stroma that prevents access of systemically or intratumorally applied therapeutics. We propose a stem cell gene therapy approach for controlled tumor stroma degradation that uses the pathophysiologic process of recruitment of inflammatory cells into the tumor. This approach involves genetic modification of hematopoietic stem cells (HSCs) and their subsequent transplantation into tumor-bearing mice. We show that inducible, intratumoral expression of relaxin (Rlx) either by transplanting tumor cells that contained the Rlx gene or by transplantation of mouse HSCs transduced with an Rlx-expressing lentivirus vector delays tumor growth in a mouse model of breast cancer. The antitumor effect of Rlx was mediated through degradation of tumor stroma, which provided increased access of infiltrating antitumor immune cells to their target tumor cells. Furthermore, we have shown in a human/mouse chimeric model that genetically modified HSCs expressing a transgene can access the tumor site. Our findings are relevant for cancer gene therapy and immunotherapy.
authors.affiliation: Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA 98195, USA.
authors.forename: ZongYi
authors.initials: Z
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Sebastian
authors.initials: S
authors.lastname: Tuve
authors.forename: Ye
authors.initials: Y
authors.lastname: Xun
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Fan
authors.forename: Liang
authors.initials: L
authors.lastname: Min
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Feng
authors.forename: Nancy
authors.initials: N
authors.lastname: Kiviat
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
authors.forename: Mary Leonora
authors.initials: ML
authors.lastname: Disis
authors.forename: André
authors.initials: A
authors.lastname: Lieber