JUNE 2003

MRI measures response to gene therapy of HCC

By: Paula Gould

CONTEXT: Gene therapy has attracted attention as a possible means to selectively attack cancer cells without harming healthy tissue. University of Hamburg researchers have developed a method to boost the immune response against hepatocellular carcinoma. Results from early animal experiments measured with MRI tumor volumetry indicate that the approach holds promise for more successfully treating this tenacious disease.

RESULTS: Dr. Gerrit Krupski, a professor of radiology at University Hospital Hamburg, and colleagues from the departments of medicine and molecular biology implanted malignant HCC cells in the livers of adult rats. MRI was performed nine days later to establish base measures of tumor volume. On day 14, control animals were injected with a "fake" treatment (109 particles of vector Ad-GFP). Rats in the treatment groups received one of three doses: either 107, 108, or 109 infectious viral particles of an Ad-3 vector, expressing mouse interleukin-2 and -12 and the 4-1BB ligand injected directly into the tumor.

MRI tumor volumetry, performed again on days 14 and 26, revealed constant tumor growth in the control group rats following administration of Ad-GFP (mean tumor volume increased 625% compared with day 14 baseline). Tumors in all rats from each treatment group, however, shrank after gene therapy, with the extent of volume reduction corresponding to dose.

IMPLICATIONS: Tumor growth reduction correlates with the amount of inoculated viral particles and will form the basis for future gene therapy experiments, according to a poster presented by Krupski and colleagues at the 2003 European Congress of Radiology.