Toward a stem cell gene therapy for breast cancer

ZongYi Li, Ying Liu, Sebastian Tuve, Ye Xun, Xiaolong Fan, Liang Min, Qinghua Feng, Nancy Kiviat, Hans-Peter Kiem, Mary Leonora Disis, Andre Lieber

Research output: Contribution to journalArticlepeer-review

26 Citations (SciVal)

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. (Blood. 2009; 113: 5423-5433)
Original languageEnglish
Pages (from-to)5423-5433
JournalBlood
Volume113
Issue number22
DOIs
Publication statusPublished - 2009

Subject classification (UKÄ)

  • Hematology

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