@article{b0f653c89de24953b7888c620de41f59,
title = "Enhanced adenovirus infection of melanoma cells by fiber-modification: Incorporation of RGD peptide or Ad5/3 chimerism",
abstract = "The incidence of malignant melanoma has been increasing. Unfortunately, advanced melanomas are rarely curable with standard therapy; therefore, new forms of treatment such as gene therapy are needed. The success of gene delivery or oncolysis depends on the nature of the vector. Adenoviral vectors are advantageous for several reasons; however, they are dependent on CAR (coxsackie and adenovirus receptor) which is deficient or heterogeneously expressed on melanoma cells in situ. Correspondingly, transduction of freshly purified melanoma cells has been shown to be minimal or variable. In order to overcome this shortcoming, it is necessary to construct tropism modified adenoviral vectors. With this goal in mind, we generated two tropism modified vectors, Ad5lucRGD which has an RGD motif incorporated into the HI loop of the fiber knob and Ad5/3luc1 which contains the tail and shaft domain of the Ad5 fiber and the knob domain of the Ad3 fiber. Herein we demonstrate that Ad5/3luc1 infects CAR-negative primary melanoma cells 1128 times better than Ad5luc1 and 34 times better than Ad5lucRGD. Furthermore we show that Ad5/3luc1 and Ad5lucRGD infect via a CAR independent route by blocking the CAR receptor. In addition, we show that the infectivity of the cells correlates with the expression of CAR and Ad3 receptors determined by FACS analysis. Therefore, Ad5/3 is very attractive as a potential therapeutic vector for malignant melanoma.",
keywords = "Adenovirus vectors, Fiber chimerism, Gene therapy, Infectivity enhancement, Melanoma, RGD peptide",
author = "Volk, {Andrea L.} and Rivera, {Angel A.} and Anna Kanerva and Gerd Bauerschmitz and Igor Dmitriev and Nettelbeck, {Dirk M.} and Curiel, {David T.}",
note = "Funding Information: Malignant neoplasms of the skin including basal cell carcinoma, squamous cell carci-noma and malignant melanoma, are the most common cancers in humans.1The incidence of both melanoma and nonmelanoma skin cancer is increasing. However, the incidence of malignant melanoma is increasing more rapidly than any other type of cancer,1 and approximately 44,000 new cases are diagnosed each year in the United States.2The mor-bidity and mortality from malignant melanoma is significant; accounting for up to 7,000 deaths annually in the United States.2 Furthermore, it is the leading cause of cancer deaths in women between the ages of 25 to 36 years old. Malignant melanoma is easily and suc-cessfully treated by wide local excision when the tumor is less than 1.0 mm in depth and confined to a local area. However, once the tumor has exceeded 1.0 mm in depth, patients are considered high risk for metastatic disease and sentinal node biopsy is performed in addition to wide local excision. When metastatic melanoma is evident, adjuvant therapies including therapeutic lymph node dissection, chemotherapy and radiotherapy should be This work was supported by the NIH grants considered.1 Unfortunately, metastatic melanoma is resistant to a wide range of chemo-R01 HL67962, Breast P50 CA89019, RO1 therapeutic agents and patients with distant metastases have a median survival of only 6 to CA86881, R01 AG021875, R01 CA090547, and 9 months.3,4 This has prompted investigators to search for more effective forms of by the Deutsche Forschungsgemeinschaft (grant treatment for patients with advanced disease and recurrence, including combination NE832/1 to DMN). Wewould like to acknowl- chemotherapy, biological response modifiers, vaccine immunotherapy, chemoimmuno-Facility (support provided by CFAR AIDS Coreedge the Center For Aids Research FlowCytometry therapy and gene therapy. Gene therapy has shown potential for treatment of cancer, Grant #P30A{\textcopyright} Landes Bioscience 2003. Not for distribution.I27767) and Marion Spell for provid- ing Flow Cytometry equipment and expertise, Dr. replicative vector oncolysis.5,6Several viral vectors for gene transfer have been investigated,genetic immunopotentiation, molecular chemotherapy, angiogenesis inhibition and",
year = "2003",
month = sep,
doi = "10.4161/cbt.2.5.440",
language = "English",
volume = "2",
pages = "511--515",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
number = "5",
}