LOCOREGIONAL IMMUNOTHERAPY OF MALIGNANT ASCITES BY INTRAPERITONEAL ADMINISTRATION OF OK-432 PLUS IL-2 IN GASTRIC-CANCER PATIENTS

The clinical efficacy of intraperitoneal administration of OK-432 plus interleukin-2 (IL2) for treating malignant ascites was evaluated in g astric cancer patients. Ten KE of OK-432 and 200,000 Jurkat units of I L-2 were intraperitoneally administered in tandem in the order given o n alternate days at paracentesis. Of the 22 evaluable patients, 18 (81 %) developed complete ol partial responses, showing a cytologic disapp earance of cancer cells and decrease of ascites. More than 50% of the patients obtained positive responses within 2 weeks after the initial administration of the drugs. Improvements of performance status and cl inical symptoms such as abdominal fullness, followed by restoration of oral food intake and prolongation of survival time were observed in r esponders treated with OK-432 plus IL-2. Flow cytometric analysis demo nstrated a predominant increase of the CD3(+) CD4(+) cells, especially of the CD4(+) CD45RA(-) subset, in the peritoneal cavity of the respo nders. Cytotoxicity assay after negative selection of the CD4(+) cells with the antibody and complement revealed that the CD4(+) subset poss essed cytotoxic activity against autologous tumor cells. The results s uggest that intraperitoneal administration of OK-432 plus IL-2 may not be only a practical but also an effective protocol for treating malig nant ascites in gastric cancer patients.