TNFalpha gene delivery therapy for solid tumors.
BACKGROUND
Multimodality therapy, including adjuvant and neoadjuvant chemotherapy and radiotherapy, is now the mainstay of treatment for the majority of non-hematologic cancers. Host toxicity can, however, be significant, which may contribute to local and/or systemic failures. Novel adjunctive treatments that can limit systemic exposure while synergizing with standard therapy hold promise in the fight against an increasing number of cancers.


METHODS
We discuss a TNFalpha gene delivery system used to generate high levels of intratumoral TNFalpha, while limiting systemic exposure. The delivery system utilizes a replication-deficient adenoviral vector. When injected intratumorally and activated by external beam radiation, infected cells synthesize and locally secrete large amounts of TNFalpha.


RESULTS
This review will provide the reader with a thorough understanding of the gene-based TNFalpha delivery system with special emphasis on product characteristics, mechanisms of action, clinical efficacy, safety and tolerability.


CONCLUSIONS
The TNFalpha gene delivery system holds promise as an adjunctive agent for improved local control and increasing resectability rates for many solid tumors. The completion of several ongoing randomized trials will help to better define the role for TNFalpha gene delivery therapy in the treatment of solid tumors.
Hernandez
Jonathan
J
Department of Surgery, University of South Florida, College of Medicine, The Tampa General Hospital, Center for Digestive Disorders, 1 Tampa General Circle, Tampa, Florida 33601, USA.
Cooper
Jennifer
J
Babel
Nitin
N
Morton
Connor
C
Rosemurgy
Alexander S
AS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002986:Clinical Trials as Topic; D017321:Clinical Trials, Phase I as Topic; D051765:Early Growth Response Transcription Factors / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051765:Early Growth Response Transcription Factors; D014409:Tumor Necrosis Factor-alpha