Assessment of bystander effect potency produced by intratumoral implantation of HSVtk-expressing cells using surrogate marker secretion to monitor tumor growth kinetics.

Abstract

A molecular marker, human alpha-1-antitrypsin (hAAT) was transduced into tumor cells and its secretion was found to correlate with tumor growth or regression, allowing for an accurate and continuous measurement of tumor growth kinetics. Using this system, we investigated the therapeutic potential produced purely from the bystander effect of HSVtk+ CT26 cells to eradicate established CT26 colon carcinomas in mice by direct intratumoral implantation and subsequent ganciclovir administration. With lower ratios (0.1% and 1% of initial tumor burden), tumor growth kinetics went into a static (remission) phase of approximately 2 weeks duration before relapse and resumption of progressive tumor growth. When the number of CT26tk+ modified cells injected into the tumor equaled 10% to 100% of the initial tumor cell number the bystander effect was sufficient to completely eradicate established tumors indicating that a potent bystander killing effect is produced in this system, and that a cellular therapy based on this approach may have applications.