Loss of adenoviral receptor expression in human bladder cancer cells: A potential impact on the efficacy of gene therapy

There is great interest in the development of gene therapeutic strategies f or the treatment of benign and malignant diseases, Recombinant adenovirus h as a wide spectrum of tissue specificity and is an efficient vector deliver y system. Successful gene delivery, however, requires viral entry into the target cells via specific receptor-mediated uptake, Recently, a cDNA clone (the coxsackie and adenovirus receptor [CAR]) encoding a 46-kDa protein was identified as the receptor for group C adenovirus (e,g,, adenovirus type 2 and 5), Currently, little is known regarding the expression of adenoviral receptor in normal tissue and cancer, In this paper, we have documented a s ignificant difference in viral receptor levels that may be due to transcrip tional regulation of the CAR gene in several human bladder cancer cell line s. The differences in viral receptor levels in these cells correlated with their sensitivity to viral infection. Transfection of receptor-negative cel l line with CAR cDNA led to increased virus binding and increased susceptib ility to adenovirus-mediated gene delivery. Our results demonstrate that th e expression of adenoviral receptor is variable among human bladder cancer cells. This variability may have a significant impact on the outcome of ade novirus-based gene therapy.