High-capacity adenovirus vector-mediated anti-glioma gene therapy in the presence of systemic antiadenovirus immunity.
Gene therapy is proposed as a novel therapeutic strategy for treating glioblastoma multiforme (GBM), a devastating brain cancer. In the clinic, antivector immune responses pose formidable challenges. Herein we demonstrate that high-capacity adenovirus vectors (HC-Ads) carrying the conditional cytotoxic gene herpes simplex virus type 1-thymidine kinase (TK) induce tumor regression and long-term survival in an intracranial glioma model, even in the presence of systemic antiadenovirus immunity, as could be encountered in patients. First-generation Ad-TK failed to elicit tumor regression in this model. These results pave the way for implementing HC-Ad-TK-mediated gene therapy as a powerful adjuvant for treating GBM.
King
Gwendalyn D
GD
Board of Governors Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis Bldg., Research Pavilion, Rm. 5090, Los Angeles, CA 90048, USA. castromg@cshs.org
Muhammad
A K M Ghulam
AK
Xiong
Weidong
W
Kroeger
Kurt M
KM
Puntel
Mariana
M
Larocque
Daniel
D
Palmer
Donna
D
Ng
Philip
P
Lowenstein
Pedro R
PR
Castro
Maria G
MG
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000628:therapy; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use*; D005909:Glioblastoma / Q000628:therapy*; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006801:Humans; D051381:Rats; D011917:Rats, Inbred Lew; D015996:Survival Rate; D013937:Thymidine Kinase / Q000235:genetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D000914:Antibodies, Viral; D013937:Thymidine Kinase