PMID- 7834119 OWN - NLM STAT- MEDLINE DCOM- 19950227 LR - 20210103 IS - 1067-5582 (Print) IS - 1067-5582 (Linking) VI - 16 IP - 3 DP - 1994 Oct TI - Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial. PG - 198-210 AB - A pilot study was conducted in patients who had advanced epithelial ovarian carcinoma, and who were refractory to platinum-based chemotherapy, to determine the feasibility and clinical effects of a schedule of intraperitoneal (IP) tumor-infiltrating lymphocytes (TIL) expanded in recombinant interleukin-2 (rIL-2), and low-dose rIL-2 IP. TIL were expanded from solid metastases or malignant effusions in serum-free AIM V medium supplemented with low concentrations (600 IU/ml) or rIL-2 using a four-step method of expansion that included a hollow fiber bioreactor (artificial capillary culture system). Patients received IP TIL suspended in dextrose 5% in sodium chloride 0.2% containing 0.1% human albumin and 6 x 10(5) IU rIL-2 on day 1, followed by 6 x 10(5) IU rIL-2/m2 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 IP rIL-2 were administered. Patients (n = 3) whose TIL failed to grow in vitro received IP IL-2 alone. Eight patients received rIL-2 expanded TIL (10(10)-10(11) range) plus rIL-2 followed by several cycles of rIL-2 alone. One of these patients was treated twice with TIL plus rIL-2. Expanded TIL were primarily CD3+CD4+TCR alpha beta+ (eight TIL-derived T-cell lines). One TIL-derived T-cell line was comprised mostly of CD3+CD8+TCR alpha beta+ cells. Eleven patients (eight treated with TIL plus rIL-2 and three patients 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 cycle was 4 days long. Grade 3 anemia occurred in 1 of 9 TIL plus rIL-2 cycles and 3 of 38 cycles of rIL-2 alone. There were no measurable responses; however, four of eight patients treated with IP TIL plus rIL-2 had some indication of clinical activity: ascites regression (two patients), tumor and CA-125 reduction (one patient), and surgically confirmed stable tumor and CA-125 values (one patient). The schedule of IP TIL plus low-dose rIL-2 shows manageable toxicity and is worthy of further evaluation in patients with epithelial ovarian cancer who have less tumor burden. FAU - Freedman, R S AU - Freedman RS AD - Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston. FAU - Edwards, C L AU - Edwards CL FAU - Kavanagh, J J AU - Kavanagh JJ FAU - Kudelka, A P AU - Kudelka AP FAU - Katz, R L AU - Katz RL FAU - Carrasco, C H AU - Carrasco CH FAU - Atkinson, E N AU - Atkinson EN FAU - Scott, W AU - Scott W FAU - Tomasovic, B AU - Tomasovic B FAU - Templin, S AU - Templin S AU - et al. LA - eng GR - CA 57884/CA/NCI NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunother Emphasis Tumor Immunol JT - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy JID - 9418950 RN - 0 (Interleukin-2) RN - 0 (Recombinant Proteins) SB - IM MH - Adult MH - Aged MH - Cell Line MH - Female MH - Humans MH - Immunotherapy, Adoptive/*methods MH - Injections, Intraperitoneal MH - Interleukin-2/adverse effects/*therapeutic use MH - Lymphocytes, Tumor-Infiltrating/*transplantation MH - Middle Aged MH - Ovarian Neoplasms/*therapy MH - Peritoneal Neoplasms/secondary/therapy MH - Pilot Projects MH - Recombinant Proteins/adverse effects/therapeutic use MH - T-Lymphocytes/immunology EDAT- 1994/10/01 00:00 MHDA- 1994/10/01 00:01 CRDT- 1994/10/01 00:00 PHST- 1994/10/01 00:00 [pubmed] PHST- 1994/10/01 00:01 [medline] PHST- 1994/10/01 00:00 [entrez] AID - 10.1097/00002371-199410000-00004 [doi] PST - ppublish SO - J Immunother Emphasis Tumor Immunol. 1994 Oct;16(3):198-210. doi: 10.1097/00002371-199410000-00004.