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Laboratory of Experimental Urology, Nijmegen Center of Molecular Life Sciences, University Medical Center Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, the Netherlands
Department of Urology, University Medical Center Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, the Netherlands
Letter
In their article, Haviv et al. (1)
suggested that gene therapy for renal cancer with the conventional serotype 5 adenoviral vectors is limited due to a deficiency in expression of the CAR1
on RCC cells. Subsequently, they suggested and described the use of alternative adenoviral vectors targeted to the subgroup B adenovirus receptor or to the 
v integrins more abundantly expressed on RCC cells. Unfortunately, their study was only performed on established RCC cell lines, whereas more relevant primary RCC cell cultures were not included. We have previously analyzed the adenoviral transduction of several established RCC cell lines and primary cell cultures with recombinant serotype 5 adenovirus expressing the green fluorescent protein marker gene, Ad5-GFP. Almost complete transduction of six RCC cell lines (SKRC-1, SKRC-7, SKRC-10, SKRC-17, SKRC-59, and CaKi-1) was achieved at MOI levels between 1 and 10 (Fig. 1A)
, although a dichotomy was apparent. Moreover, highly efficient transduction at MOI = 1 was seen with four RCC primary cell cultures (EUNRC-AB, EUNRC-AR, EUNRC-8781, and EUNRC-12175) established at our institute, immediately after RCC tumor nephrectomy (Fig. 1B)
. The efficient transduction of the RCC primary cell cultures examined indicates relatively high levels of CAR expression, which was confirmed by flow cytometric analysis of CAR (Fig. 2)
. In contrast, the transduction rate of dendritic cells was found to be significantly lower with 
10% of cells transduced at MOI 10 and >90% of the cells transduced at MOI 
100 (data not shown). This inefficient transduction confirmed the observation of Rea et al. (2)
showing that dendritic cells do not express CAR.
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. For instance, the RCC cell line SKRC-17 belongs to the group of cells with a high transduction rate, whereas the RCC cell line CaKi-1 belongs to the group of cells with an intermediate transduction rate. These differences correlate with the membranous CAR expression on these cells (Fig. 2)
and confirm the low CAR expression levels on the CaKi-1 cells as found by Haviv et al. (1)
.
To investigate whether the transduction efficiency of the RCC cell lines and primary cell cultures could be enhanced by targeting to the subgroup B adenovirus receptor, transduction by subgroup B (adenovirus serotype 35) fiber-modified serotype 5 adenovirus Ad5F35-GFP was studied. Such adenoviruses were found to be more efficient than conventional Ad5-GFP in transducing the CAR-negative dendritic cells (data not shown). Similarly, the RCC cell lines (SKRC-1, SKRC-10, and CaKi-1), which displayed intermediate transduction rates with Ad5-GFP, were more efficiently transduced with Ad5F35-GFP (Fig. 3A)
. In contrast, the RCC primary cell cultures (EUNRC-AB, EUNRC-AR, and EUNRC-8781) were equally susceptible for transduction by the Ad5F35-EGFP (Fig. 3B)
. In RCC cell lines with high transduction rates, no increase was observed (data not shown).
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3) examined displayed high transduction rates with serotype 5 adenovirus that could not be further improved with subgroup B fiber-modified serotype 5 adenovirus. Similar high transduction rates with serotype 5 adenovirus were seen with primary normal kidney cell cultures (data not shown). Although the number of cases examined in our study is limited, it indicates that CAR deficiency in primary RCC is not frequent. The CAR deficiency observed with some of the RCC cell lines, as also described by Haviv et al. (1)
, might be the consequence of the establishment of RCC cell line. Thus, for adenoviral gene therapy of renal cancer, retargeting to alternative cellular receptors is not required. However, the equal susceptibility for transduction of RCC cells with adenovirus serotypes 5 and 35 is an interesting finding when repeated adenoviral therapies would be considered. Then adenovirus serotype switching could be a promising approach in cancer gene therapy of RCC to overcome adenovirus serotype 5 neutralizing immune responses.
FOOTNOTES
1 The abbreviations used are: CAR, Coxsackie and adenovirus receptor; RCC, renal cell carcinoma; MOI, multiplicity of infection. 
Received 10/14/02. Accepted 2/19/03.
REFERENCES
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; SKRC-7, 
; SKRC-10, 
; SKRC-17, 
; SKRC-59, +; and CaKi-1, 
. B, RCC primary cell cultures: EUNRC-AB, 
