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.

journal_name

Blood

journal_title

Blood

authors

Li Z,Liu Y,Tuve S,Xun Y,Fan X,Min L,Feng Q,Kiviat N,Kiem HP,Disis ML,Lieber A

doi

10.1182/blood-2008-10-187237

subject

Has Abstract

pub_date

2009-05-28 00:00:00

pages

5423-33

issue

22

eissn

0006-4971

issn

1528-0020

pii

blood-2008-10-187237

journal_volume

113

pub_type

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