INTRAPERITONEAL ADOPTIVE IMMUNOTHERAPY OF OVARIAN-CARCINOMA WITH TUMOR-INFILTRATING LYMPHOCYTES AND LOW-DOSE RECOMBINANT INTERLEUKIN-2 - A PILOT TRIAL

A pilot study was conducted in patients who had advanced epithelial ov arian carcinoma, and who were refractory to platinum-based chemotherap y, to determine the feasibility and clinical effects of a schedule of intraperitoneal (IF) tumor-infiltrating lymphocytes (TIL) expanded in recombinant interleukin-2 (rIL-2), and low-dose rIL-2 IF. TIL were exp anded from solid metastases or malignant effusions in serum-free AIM V medium supplemented with low concentrations (600 IU/ml) of rIL-2 usin g a four-step method of expansion that included a hollow fiber bioreac tor (artificial capillary culture system). Patients received IP TIL su spended in dextrose 5% in sodium chloride 0.2% containing 0.1% human a lbumin and 6 x 10(5) IU rIL-2 on day 1, followed by 6 x 10(5) IU rIL-2 /m(2) body surface area, administered daily by bolus IP injection, on days 2-4, 8-11, and 15-18. In the absence of disease progression, two additional 4-day cycles of LP rIL-2 were administered. Patients (n = 3 ) whose TIL failed to grow in vitro received IP IL-2 alone. Eight pati ents received rIL-2 expanded TIL (10(10)-10(11) range) plus rIL-2 foll owed by several cycles of rIL-2 alone. One of these patients was treat ed twice with TIL plus rIL-2. Expanded TIL were primarily CD3(+) CD4() CTR alpha beta(+) (eight TIL-derived T-cell lines). One TIL-derived T-cell line was comprised mostly of CD3(+) CD8(+) TCR alpha beta(+) ce lls. Eleven patients (eight treated with TIL plus rIL-2 and three pati ents treated with rIL-2 alone) received a total of 38 cycles of rIL-2 without TIL. Grade 3 clinical toxicity (peritonitis) occurred in 1 of 9 cycles of TIL plus rIL-2 and 1 of 38 cycles of rIL-2 alone. Each cyc le was 4 days long. Grade 3 anemia occurred in 1 of 9 TIL plus rIL-2 c ycles and 3 of 38 cycles of rIL-2 alone. There were no measurable resp onses; however, four of eight patients treated with IP TIL plus rIL-2 had some indication of clinical activity: ascites regression (two pati ents), tumor and CA-125 reduction (one patient), and surgically confir med stable tumor and CA-125 values (one patient). The schedule of IP T IL plus low-dose rIL-2 shows manageable toxicity and is worthy of furt her evaluation in patients with epithelial ovarian cancer who have les s tumor burden.