10873077

pubmed:Citation

6

To identify strategies that enhance tumor-specific immunity in patients with ovarian carcinoma, 22 patients received four to six doses of i.p. recombinant IFN-gamma (rIFN-gamma), 200 microg/m2 on days 1, 3, 5, 8, 10, and 12, and i.p. recombinant interleukin 2 (rIL-2), either 6.0 x 10(5) IU/m2 (group A) or 1.0 x 10(5) IU/m2 (group B), on days 9, 10, and 11. Two patients in group A also received T-cell lines expanded from peritoneal tumor-infiltrating lymphocytes (TILs) obtained after i.p. rIFN-gamma/rIL-2 administration. Toxicity was manageable and included five nonhematological grade 3 or 4 events in 22 patients (23%). A patient had normalization of CA-125 values and a progression-free interval of 18 months, after receiving i.p. rIFN-gamma/rIL-2 without TILs. Another patient who received i.p. rIFN-gamma/rIL-2 plus TILs had stabilization of ascites and intra-abdominal tumors and >50% reduction in serum CA-125 values over 6 months. A third patient who received i.p. rIFN-gamma/rIL-2 had stabilization of intra-abdominal tumors and ascites accompanied by CA-125 values of 50 to 100 units over 6 months. T-cell lines for adoptive immunotherapy were developed for only 3 of 20 patients who were treated with rIFN-gamma/rIL-2. Large numbers of CD3- CD56+ adherent cells were expanded in rIL-2 in the remaining patients, precluding the development of T-cell lines. i.p. rIFN-gamma, either alone or followed by rIL-2, increased proportions of human leukocyte antigen (HLA) class I+ and class II+ tumor cells and increased HLA class I staining intensity on peritoneal carcinoma cells. i.p. rIFN-gamma plus rIL-2 also enhanced cytotoxic activity against Daudi and K562 cells and against allogeneic ovarian tumor cells. Increased cytotoxic activity was associated with an increase in the proportion of CD56+ cells. IFN-gamma and IL-2 transcripts were expressed more frequently after rIFN-gamma and rIL-2 treatment. In addition, the proportions of CD45RA+ (naive lymphocytes) were increased, and CD8+ DR+ lymphocytes were increased relative to CD8+ CD69+ cells, which were decreased. IL-10 concentrations in peritoneal fluids were increased after treatment with rIFN-gamma and the higher rIL-2 dosing (group A) but not in those treated with rIFN-gamma and the lower rIL-2 dosing (group B). These results demonstrated that patients with ovarian carcinoma can tolerate treatment with rIFN-gamma and rIL-2 and that rIFN-gamma alone or rIFN-gamma combined with rIL-2 enhances the expression of HLA class I and class II antigens on ovarian tumor cells, although immunosuppressive cytokines, such as transforming growth factor-beta and IL-10, may persist. Treatment with rIFN-gamma/rIL-2 i.p. did not facilitate the production of TIL-derived T-cell lines ex vivo.

eng

IM

MEDLINE

1078-0432

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NLM

2268-78

pubmed-meshheading:10873077-Antigens, CD3, pubmed-meshheading:10873077-Antigens, CD56, pubmed-meshheading:10873077-Ascitic Fluid, pubmed-meshheading:10873077-CA-125 Antigen, pubmed-meshheading:10873077-CD4-Positive T-Lymphocytes, pubmed-meshheading:10873077-CD8-Positive T-Lymphocytes, pubmed-meshheading:10873077-Cell Adhesion, pubmed-meshheading:10873077-Cell Membrane, pubmed-meshheading:10873077-Dose-Response Relationship, Drug, pubmed-meshheading:10873077-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:10873077-Female, pubmed-meshheading:10873077-Genes, MHC Class I, pubmed-meshheading:10873077-Genes, MHC Class II, pubmed-meshheading:10873077-Humans, pubmed-meshheading:10873077-Immunohistochemistry, pubmed-meshheading:10873077-Immunotherapy, Adoptive, pubmed-meshheading:10873077-Injections, Intraperitoneal, pubmed-meshheading:10873077-Interferon-gamma, pubmed-meshheading:10873077-Interleukin-10, pubmed-meshheading:10873077-Interleukin-2, pubmed-meshheading:10873077-K562 Cells, pubmed-meshheading:10873077-Leukocytes, Mononuclear, pubmed-meshheading:10873077-Lymphocytes, Tumor-Infiltrating, pubmed-meshheading:10873077-Neopterin, pubmed-meshheading:10873077-Ovarian Neoplasms, pubmed-meshheading:10873077-Peritoneal Neoplasms, pubmed-meshheading:10873077-RNA, Messenger, pubmed-meshheading:10873077-Recombinant Proteins, pubmed-meshheading:10873077-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10873077-Transforming Growth Factor beta, pubmed-meshheading:10873077-Transforming Growth Factor beta2, pubmed-meshheading:10873077-Tumor Cells, Cultured

Clinical and biological effects of intraperitoneal injections of recombinant interferon-gamma and recombinant interleukin 2 with or without tumor-infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma.

Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Controlled Clinical Trial