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Endostatin- and interleukin-2-expressing retroviral bicistronic vector for gene therapy of metastatic renal cell carcinoma
The journal of gene medicine, 2011-03, Vol.13 (3), p.148-157
Rocha, Flávia Gomes de Góes
Calvo, Fernanda B.
Chaves, Karen C.
Peron, Jean P. S.
Marques, Rodolfo F.
de Borba, Tânia R.
Braga, Marina S.
Pereira, Cleide B.
Vicente, Elisabete J.
Chammas, Roger
Schor, Nestor
Bellini, Maria H.
2011
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Rocha, Flávia Gomes de Góes
Calvo, Fernanda B.
Chaves, Karen C.
Peron, Jean P. S.
Marques, Rodolfo F.
de Borba, Tânia R.
Braga, Marina S.
Pereira, Cleide B.
Vicente, Elisabete J.
Chammas, Roger
Schor, Nestor
Bellini, Maria H.
Titel
Endostatin- and interleukin-2-expressing retroviral bicistronic vector for gene therapy of metastatic renal cell carcinoma
Ist Teil von
The journal of gene medicine, 2011-03, Vol.13 (3), p.148-157
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2011
Quelle
MEDLINE
Beschreibungen/Notizen
Background Metastatic renal cell carcinoma (mRCC) is one of the most treatment‐resistant malignancies. Despite all new therapeutic advances, almost all patients develop resistance to treatment and cure is rarely seen. In the present study, we evaluated the antitumor effect of a bicistronic retrovirus vector encoding both endostatin (ES) and interleukin (IL)‐2 using an orthotopic metastatic RCC mouse model. Methods Balb/C‐bearing Renca cells were treated with NIH/3T3‐LendIRES‐IL‐2‐SN cells. In the survival studies, mice were monitored daily until they died. At the end of the in vivo experiment, serum levels of IL‐2 and ES were measured, the lung was weighed, and the number of metastatic nodules, nodule area, tumor vessels and proliferation of tumor‐infiltrating Renca cells were determined. Results Inoculation of NIH/3T3‐LendIRES‐IL‐2‐SN cells resulted in an increase in ES and IL‐2 levels in the treated group (p < 0.05). There was a significant decrease in lung wet weight, lung nodule area and tumor vessels in the treated group compared to the control group (p < 0.001). The proliferation of Renca cells in the bicistronic‐treated group was significantly reduced compared to the control group (p < 0.05). Kaplan–Meier survival curves showed that the probability of survival was significantly higher for mice submitted to bicistronic therapy (log‐rank test, p = 0.0016). Bicistronic therapy caused an increase in the infiltration of CD4, CD4 interferon (IFN)γ‐producing, CD8, CD8 IFNγ‐producing and natural killer (CD49b) cells. Conclusions Retroviral bicistronic gene transfer led to the secretion of functional ES and IL‐2 that was sufficiently active to: (i) inhibit tumor angiogenesis and tumor cell proliferation and (ii) increase the infiltration of immune cells. Copyright © 2011 John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 1099-498X, 1521-2254
eISSN: 1521-2254
DOI: 10.1002/jgm.1547
Titel-ID: cdi_proquest_miscellaneous_883027901
Format
–
Schlagworte
Animals
,
Carcinoma, Renal Cell - blood supply
,
Carcinoma, Renal Cell - mortality
,
Carcinoma, Renal Cell - secondary
,
Carcinoma, Renal Cell - therapy
,
Cell Line
,
Cell Proliferation
,
Disease Models, Animal
,
endostatin
,
Endostatins - blood
,
Endostatins - genetics
,
Endostatins - secretion
,
Gene therapy
,
Genetic Therapy
,
Genetic Vectors - genetics
,
Humans
,
interleukin-2
,
Interleukin-2 - blood
,
Interleukin-2 - genetics
,
Interleukin-2 - secretion
,
Kaplan-Meier Estimate
,
Kidney Neoplasms - blood supply
,
Kidney Neoplasms - mortality
,
Kidney Neoplasms - pathology
,
Kidney Neoplasms - therapy
,
Lung Neoplasms - blood supply
,
Lung Neoplasms - mortality
,
Lung Neoplasms - secondary
,
Lung Neoplasms - therapy
,
Male
,
Mice
,
Mice, Inbred BALB C
,
Neovascularization, Pathologic - prevention & control
,
Random Allocation
,
retroviral bicistronic vector
,
Retroviridae - genetics
,
Retrovirus
,
Tumor Burden
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