Effects of interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) association in intraperitoneal radioimmunotherapy: studies on an in vitro micrometastasis model.

ABSTRACT

We considered the usefulness of an association of two cytokines interferon gamma (INF gamma) and tumor necrosis factor alpha (TNF alpha) in optimizing intraperitoneal (i.p.) radioimmunotherapy of ovarian cancer. Studies were performed in conditions similar to those observed in vivo, using tumor multicell spheroids of the SHIN-3 ovarian adenocarcinoma line which expresses CA125 and O3 antigens. Light and electron microscopy showed that this cytokine association caused considerable modification of the three-dimensional morphology of the spheroids and the cells composing them. The uptake and retention kinetics of 125I-labeled F(ab')2 fragments of OC125 and OVTL-3 antibodies indicated that the presence of the cytokines led to a 1.5-fold increase in the quantity of O3 antigen at the spheroid surface. These results were confirmed by autoradiographs showing that the INF gamma-TNF alpha association produced extensive direct antitumor action, with better penetration and uptake of OVTL-3 antibody. Thus, i.p. radioimmunotherapy of micrometastases could be optimized by an initial injection of the IFN gamma-TNF alpha combination.