Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium.
OBJECTIVE
Spinal cord tumours are highly malignant and often lead to paralysis and death due to their infiltrative nature, high recurrence rate and limited treatment options. In this study, we measured antitumour efficacy of the Salmonella typhimurium A1-R tumour-targeting bacterium strain, administered systemically or intrathecally, to spinal cord cancer in orthotopic mouse models.


METHODS
Tumour fragments of U87-RFP were implanted by surgical orthotopic implantation into the dorsal site of the spinal cord. Five and 10 days after transplantation, eight mice in each group were treated with A1-R (2 x 10(7) CFU/200 microL i.v. injection or 2 x 10(6) CFU/10 microL intrathecal injection).


RESULTS
Untreated mice showed progressive paralysis beginning at day 6 after tumour transplantation and developed complete paralysis between 18 and 25 days. Mice treated i.v. with A1-R had onset of paralysis at approximately 11 days and at 30 days; five mice developed complete paralysis, while the other three mice had partial paralysis. Mice treated by intrathecal injection of A1-R had onset of paralysis at approximately 18 days and one mouse was still not paralysed at day 30. Only one mouse developed complete paralysis at day 30 in this group. Intrathecally treated animals had a significantly better survival than the i.v. treated group as well as over the control group.


CONCLUSIONS
These results suggest that S. typhimurium A1-R monotherapy can effectively treat spinal cord glioma.
Kimura
H
H
AntiCancer, Inc., San Diego, CA, USA.
Zhang
L
L
Zhao
M
M
Hayashi
K
K
Tsuchiya
H
H
Tomita
K
K
Bouvet
M
M
Wessels
J
J
Hoffman
R M
RM
D000818:Animals; D001691:Biological Therapy / Q000379:methods; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000628:therapy*; D006801:Humans; D007278:Injections, Spinal; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D030781:Organisms, Genetically Modified; D010243:Paralysis / Q000209:etiology / Q000628:therapy; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D013120:Spinal Cord Neoplasms / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays; D000070584:Tripartite Motif Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins