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Toward a stem cell gene therapy for breast cancer

Li, ZongYi; Liu, Ying; Tuve, Sebastian; Xun, Ye; Fan, Xiaolong LU ; Min, Liang; Feng, Qinghua; Kiviat, Nancy; Kiem, Hans-Peter and Disis, Mary Leonora, et al. (2009) In Blood 113(22). p.5423-5433
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... (More)
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) (Less)
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Contribution to journal
publication status
published
subject
in
Blood
volume
113
issue
22
pages
5423 - 5433
publisher
American Society of Hematology
external identifiers
  • wos:000266634700013
  • scopus:67049164937
ISSN
1528-0020
DOI
10.1182/blood-2008-10-187237
language
English
LU publication?
yes
id
dbf29c4e-5466-4d58-80fe-fe0df3287b23 (old id 1444113)
date added to LUP
2009-07-17 09:45:22
date last changed
2017-04-16 03:36:07
@article{dbf29c4e-5466-4d58-80fe-fe0df3287b23,
  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)},
  author       = {Li, ZongYi and Liu, Ying and Tuve, Sebastian and Xun, Ye and Fan, Xiaolong and Min, Liang and Feng, Qinghua and Kiviat, Nancy and Kiem, Hans-Peter and Disis, Mary Leonora and Lieber, Andre},
  issn         = {1528-0020},
  language     = {eng},
  number       = {22},
  pages        = {5423--5433},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Toward a stem cell gene therapy for breast cancer},
  url          = {http://dx.doi.org/10.1182/blood-2008-10-187237},
  volume       = {113},
  year         = {2009},
}