This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Freedman, R. S. Articles by Platsoucas, C. D. Search for Related Content PubMed PubMed Citation Articles by Freedman, R. S. Articles by Platsoucas, C. D.

Clinical and Biological Effects of Intraperitoneal Injections of Recombinant Interferon- and Recombinant Interleukin 2 with or without Tumor-infiltrating Lymphocytes in Patients with Ovarian or Peritoneal Carcinoma¹

Departments of Gynecologic Oncology [R. S. F., C. L. E., M. N., B. M., R. P., S. T., W. S.], Internal Medicine Specialties [A. P. K., J. J. K., C. V.], and Biomathematics[L. L., E. N. A.], and Pathology Image Analysis Laboratory[H-Z. Z.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 [C. D. P.]

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- (rIFN-), 200 µg/m² on days 1, 3, 5, 8, 10, and 12, and i.p. recombinant interleukin 2 (rIL-2), either 6.0 x 10⁵ IU/m² (group A) or 1.0 x 10⁵ 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-/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-/rIL-2 without TILs. Another patient who received i.p. rIFN-/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-/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-/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-, 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- 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- and IL-2 transcripts were expressed more frequently after rIFN- 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- and the higher rIL-2 dosing (group A) but not in those treated with rIFN- and the lower rIL-2 dosing (group B). These results demonstrated that patients with ovarian carcinoma can tolerate treatment with rIFN- and rIL-2 and that rIFN- alone or rIFN- 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-ß and IL-10, may persist. Treatment with rIFN-/rIL-2 i.p. did not facilitate the production of TIL-derived T-cell lines ex vivo.

This article has been cited by other articles:

				P. Rolland, S. Deen, I. Scott, L. Durrant, and I. Spendlove Human Leukocyte Antigen Class I Antigen Expression Is an Independent Prognostic Factor in Ovarian Cancer Clin. Cancer Res., June 15, 2007; 13(12): 3591 - 3596. [Abstract] [Full Text] [PDF]

				G. C. Cesana, F. Romano, G. Piacentini, M. Scotti, A. Brenna, G. Bovo, M. Vaghi, G. Aletti, R. Caprotti, H. Kaufman, et al. Low-dose Interleukin-2 Administered Pre-operatively to Patients with Gastric Cancer Activates Peripheral and Peritumoral Lymphocytes But Does Not Affect Prognosis Ann. Surg. Oncol., April 1, 2007; 14(4): 1295 - 1304. [Abstract] [Full Text] [PDF]

				E. Esplugues, D. Sancho, J. Vega-Ramos, C. Martinez-A, U. Syrbe, A. Hamann, P. Engel, F. Sanchez-Madrid, and P. Lauzurica Enhanced Antitumor Immunity in Mice Deficient in CD69 J. Exp. Med., May 5, 2003; 197(9): 1093 - 1106. [Abstract] [Full Text] [PDF]

				L. Zhang, J. R. Conejo-Garcia, D. Katsaros, P. A. Gimotty, M. Massobrio, G. Regnani, A. Makrigiannakis, H. Gray, K. Schlienger, M. N. Liebman, et al. Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer N. Engl. J. Med., January 16, 2003; 348(3): 203 - 213. [Abstract] [Full Text] [PDF]

				R. Lenzi, M. Rosenblum, C. Verschraegen, A. P. Kudelka, J. J. Kavanagh, M. E. Hicks, E. A. Lang, M. A. Nash, L. B. Levy, M. E. Garcia, et al. Phase I Study of Intraperitoneal Recombinant Human Interleukin 12 in Patients with Mullerian Carcinoma, Gastrointestinal Primary Malignancies, and Mesothelioma Clin. Cancer Res., December 1, 2002; 8(12): 3686 - 3695. [Abstract] [Full Text] [PDF]