Bystander effect in the adenovirus-mediated wild-type p53 gene therapy model of human squamous cell carcinoma of the head and neck

In models of human lung and head and neck cancer, there have been anecdotal reports of a bystander effect in wild-type p53 gene therapy, an apoptosis-inducing molecular intervention strategy. These reports do not definitively demonstrate the presence of a bystander effect, nor do they elucidate requirements for or characteristics of this phenomenon. We have investigated human squamous cell carcinoma of the head and neck for the presence and requirements of a bystander effect after wild-type p53 gene transduction. Recombinant adenovirus, Ad-p53, was used for wild-type p53 gene transfers. To investigate the role of intercellular contact between p53- transduced and nontransduced cells in mediating a growth inhibitory (bystander) effect on nontransduced cells, coculturing experiments were conducted on human squamous cell carcinoma of the head and neck cell lines TU138 and TU167. For TU138, 29% growth inhibition of nontransduced cells was demonstrated 3 days after p53-transduced and nontransduced cells were cocultured with intercellular contact. This growth inhibition was abolished when cells were cocultured without intercellular contact. TU167 did not demonstrate a bystander effect under any coculturing condition. Supernatant from Ad-p53-infected TU138 and TU167 cells demonstrated no growth-inhibitory effect on respective nontransduced cells. The bystander effect in the adenovirus-mediated wild-type p53 gene therapy model of squamous cell carcinoma of the head and neck, when present, requires intercellular contact. Possible mechanisms of the observed in vitro bystander effect are discussed.