EFFECTS OF INTERFERON-GAMMA (IFN-GAMMA) AND TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) ASSOCIATION IN INTRAPERITONEAL RADIOIMMUNOTHERAPY - STUDIES ON AN IN-VITRO MICROMETASTASIS MODEL

We considered the usefulness of an association of two cytokines interf eron 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 vi vo, using tumor multicell spheroids of the SHIN-3 ovarian adenocarcino ma line which expresses CA125 and O3 antigens. Light and electron micr oscopy showed that this cytokine association caused considerable modif ication of the three-dimensional morphology of the spheroids and the c ells composing them. The uptake and retention kinetics of I-125-labele d F(ab')(2) fragments of OC125 and OVTL-3 antibodies indicated that th e 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 b y autoradiographs showing that the INF gamma-TNF alpha association pro duced extensive direct antitumor action, with better penetration and u ptake of OVTL-3 antibody. Thus, i.p. radioimmunotherapy of micrometast ases could be optimized by an initial injection of the INF gamma-TNF a lpha combination.