PMID- 10873077
OWN - NLM
STAT- MEDLINE
DCOM- 20001207
LR  - 20171116
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 6
IP  - 6
DP  - 2000 Jun
TI  - 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.
PG  - 2268-78
AB  - 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.
FAU - Freedman, R S
AU  - Freedman RS
AD  - Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer 
      Center, Houston 77030, USA.
FAU - Kudelka, A P
AU  - Kudelka AP
FAU - Kavanagh, J J
AU  - Kavanagh JJ
FAU - Verschraegen, C
AU  - Verschraegen C
FAU - Edwards, C L
AU  - Edwards CL
FAU - Nash, M
AU  - Nash M
FAU - Levy, L
AU  - Levy L
FAU - Atkinson, E N
AU  - Atkinson EN
FAU - Zhang, H Z
AU  - Zhang HZ
FAU - Melichar, B
AU  - Melichar B
FAU - Patenia, R
AU  - Patenia R
FAU - Templin, S
AU  - Templin S
FAU - Scott, W
AU  - Scott W
FAU - Platsoucas, C D
AU  - Platsoucas CD
LA  - eng
GR  - MO1-RR-02558/RR/NCRR NIH HHS/United States
GR  - R01 CA-64943/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (CA-125 Antigen)
RN  - 0 (CD3 Complex)
RN  - 0 (CD56 Antigen)
RN  - 0 (Interleukin-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TGFB2 protein, human)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta2)
RN  - 130068-27-8 (Interleukin-10)
RN  - 670-65-5 (Neopterin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Ascitic Fluid/metabolism
MH  - CA-125 Antigen/blood
MH  - CD3 Complex/biosynthesis
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - CD56 Antigen/biosynthesis
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism
MH  - Cell Adhesion
MH  - Cell Membrane/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Genes, MHC Class I
MH  - Genes, MHC Class II
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunotherapy, Adoptive
MH  - Injections, Intraperitoneal
MH  - Interferon-gamma/*pharmacology
MH  - Interleukin-10/biosynthesis
MH  - Interleukin-2/*pharmacology
MH  - K562 Cells
MH  - Leukocytes, Mononuclear/immunology/metabolism
MH  - Lymphocytes, Tumor-Infiltrating/immunology/*metabolism
MH  - Neopterin/biosynthesis
MH  - Ovarian Neoplasms/*drug therapy/immunology
MH  - Peritoneal Neoplasms/*drug therapy/immunology
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins/*pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transforming Growth Factor beta/biosynthesis
MH  - Transforming Growth Factor beta2
MH  - Tumor Cells, Cultured
EDAT- 2000/06/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/06/29 11:00
PHST- 2000/06/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/06/29 11:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 2000 Jun;6(6):2268-78.