Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma.
OBJECTIVE
Alternative and complementary therapeutic strategies need to be developed for metastatic breast cancer. Virotherapy is a novel therapeutic approach for the treatment of cancer in which the replicating virus itself is the anticancer agent. However, the success of virotherapy has been limited due to inefficient virus delivery to the tumor site. The present study addresses the utility of human mesenchymal stem cells (hMSCs) as intermediate carriers for conditionally replicating adenoviruses (CRAds) to target metastatic breast cancer in vivo.


METHODS
HMSC were transduced with CRAds. We used a SCID mouse xenograft model to examine the effects of systemically injected CRAd loaded hMSC or CRAd alone on the growth of MDA-MB-231 derived pulmonary metastases (experimental metastases model) in vivo and on overall survival.


RESULTS
Intravenous injection of CRAd loaded hMSCs into mice with established MDA-MB-231 pulmonary metastatic disease homed to the tumor site and led to extended mouse survival compared to mice treated with CRAd alone.


CONCLUSIONS
Injected hMSCs transduced with CRAds suppressed the growth of pulmonary metastases, presumably through viral amplification in the hMSCs. Thus, hMSCs may be an effective platform for the targeted delivery of CRAds to distant cancer sites such as metastatic breast cancer.
Stoff-Khalili
Mariam A
MA
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, 901 19th Street South, BMR2 502, Birmingham, AL 35294-2172, USA.
Rivera
Angel A
AA
Mathis
J Michael
JM
Banerjee
N Sanjib
NS
Moon
Amanda S
AS
Hess
A
A
Rocconi
Rodney P
RP
Numnum
T Michael
TM
Everts
M
M
Chow
Louise T
LT
Douglas
Joanne T
JT
Siegal
Gene P
GP
Zhu
Zeng B
ZB
Bender
Hans Georg
HG
Dall
Peter
P
Stoff
Alexander
A
Pereboeva
Larissa
L
Curiel
David T
DT
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D059630:Mesenchymal Stem Cells; D051379:Mice; D016513:Mice, SCID; D011401:Promoter Regions, Genetic; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D019718:Receptors, CXCR4