Portal de Periódicos da CAPES

A RANDOMIZED PHASE II TRIAL COMPARING TWO DIFFERENT SEQUENCE COMBINATIONS OF AUTOLOGOUS VACCINE AND HUMAN RECOMBINANT INTERFERON γ AND HUMAN RECOMBINANT INTERFERON α2B THERAPY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA: CLINICAL OUTCOME AND ANALYSIS OF IMMUNOLOGICAL PARAMETERS

2000; Lippincott Williams & Wilkins; Volume: 163; Issue: 4 Linguagem: Inglês

10.1016/s0022-5347(05)67771-3

1527-3792

Thomas Schwaab, John A. Heaney, Alan R. Schned, Robert D. Harris, Bernard F. Cole, Randolph J. Noelle, DOROTHY M. PHILLIPS, LAURA STEMPKOWSKI, Marc S. Ernstoff,

CAR-T cell therapy research

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Apr 2000A RANDOMIZED PHASE II TRIAL COMPARING TWO DIFFERENT SEQUENCE COMBINATIONS OF AUTOLOGOUS VACCINE AND HUMAN RECOMBINANT INTERFERON γ AND HUMAN RECOMBINANT INTERFERON α2B THERAPY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA: CLINICAL OUTCOME AND ANALYSIS OF IMMUNOLOGICAL PARAMETERS THOMAS SCHWAAB, JOHN A. HEANEY, ALAN R. SCHNED, ROBERT D. HARRIS, BERNARD F. COLE, RANDOLPH J. NOELLE, DOROTHY M. PHILLIPS, LAURA STEMPKOWSKI, and MARC S. ERNSTOFF THOMAS SCHWAABTHOMAS SCHWAAB , JOHN A. HEANEYJOHN A. HEANEY , ALAN R. SCHNEDALAN R. SCHNED , ROBERT D. HARRISROBERT D. HARRIS , BERNARD F. COLEBERNARD F. COLE , RANDOLPH J. NOELLERANDOLPH J. NOELLE , DOROTHY M. PHILLIPSDOROTHY M. PHILLIPS , LAURA STEMPKOWSKILAURA STEMPKOWSKI , and MARC S. ERNSTOFFMARC S. ERNSTOFF View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)67771-3AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The clinical observation of spontaneous regression in patients with renal cell carcinoma (RCC) and the response to various immunotherapeutic therapies strongly suggest a role for the host immune system in this disease. Prior studies showed that sequential administration of interferon (IFN) γ and IFN α to RCC patients was safe. Clinical responses as well as immune changes in the peripheral blood mononuclear cell compartment were observed. Autologous tumor cell vaccines (AV) have also demonstrated activity in renal cell carcinoma. We hypothesize that the addition of AV to sequential IFN γ and α therapy might improve the tumor-specific immune response by providing an appropriate source of antigen in the appropriate cytokine environment. To our knowledge, this is the first trial using AV combined with IFN α and IFN γ. The purpose of this study was to evaluate the feasibility of manufacturing and administering (AV) from resected tumor samples, and administration of AV with combination IFN γ and IFN α therapy. Finally, the impact on immunological parameters of these treatment options was assessed. Materials and Methods: Patients with metastatic RCC were randomly assigned to receive AV plus bCG along with a sequential administration of IFN γ and α either together or after initiation of vaccine. Toxicity and clinical responses were evaluated. Modulations of the immune system were investigated by analyzing phenotype, cytokine mRNA expression, T cell proliferation and cytotoxicity in the peripheral blood mononuclear cell compartment. Results: Fourteen patients with metastatic renal cell carcinoma were enrolled in this study; 9 were available for response evaluation. In a 70 day period, 3 (33%) showed mixed responses, 5 (56%) stable disease and 1 (11%) progression of disease. Toxicities were consistent with previous clinical reports. In the flow-cytometry phenotype analysis, stimulation of distinct subsets of circulating T-lymphocytes and a decrease of CD8+ T cell subsets was demonstrated. T-cell proliferation to allogeneic tumor cell stimulation improved following treatment. IL-4 and IL-5 mRNA levels were reduced in all patients after treatment. Patients who responded to treatment did not produce any IL-4 mRNA at all, before or after treatment. Conclusions: AV with IFNγ and IFNα therapy might induce a MHC class-mediated cytotoxic T lymphocyte (CTL) response. We suggest that adequate therapy might direct T cell response toward a Th1 type response. We hypothesize a state of improved immune readiness in patients who might eventually respond to immunotherapy. References 1 : Renal cell carcinoma: recent progress and future directions. Cancer Res1997; 57: 5189. Google Scholar 2 : Human renal cell carcinoma as a hormone-dependent tumor. Cancer Res1978; 38: 4340. Google Scholar 3 : New prospects in the management of metastatic renal cell carcinoma. Experimental and clinical data. Uro-Oncology: Current Status and Future Trends1990; : 243. Google Scholar 4 : A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alpha in patients with metastatic renal cell carcinoma. J Clin Oncol1990; 8: 1637. Google Scholar 5 : A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. New Engl J Med1987; 316: 879. Google Scholar 6 : . Amsterdam: Elseviers Science Publishers BV1987: 432. Annual 9. Google Scholar 7 : The interaction of murine IgG subclass proteins with human monocyte Fc receptors. J Immunol1985; 135: 1299. Google Scholar 8 : Adjuvant therapy of stage IIIb melanoma with interferon alpha-2b: Clinical and immunological relevance. Dermatology1995; 191: 234. Google Scholar 9 : Interferon treatment of renal cell carcinoma. Current status and future prospects. Cancer1986; 46: 4315. Google Scholar 10 : Human recombinant interferons-beta and-gamma decrease gelatinase production and invasion by human KG-2 renal cell carcinoma cells. Int J Cancer1994; 58: 380. Google Scholar 11 : Immunological effects of treatment with sequential administration of recombinant IFN χ and α in patients with metastatic renal cell carcinoma during a phase I trial. Cancer Res1992; 52: 851. Google Scholar 12 : The treatment of renal cell carcinoma with human leukocyte alpha-interferon. J Urol1983; 130: 1063. Link, Google Scholar 13 : Recombinant alpha-2 or gamma interferon in the treatment of metastatic renal cell carcinoma: results of two phase II/III trials. Uro-Oncology: Current Status and Future Trends1990; : 275. Google Scholar 14 : Adjuvant therapy of renal cell carcinoma with active-specific-immunotherapy (ASI) using autologous tumor vaccine. Anticancer Res1997; 17: 2879. Google Scholar 15 : Specific immunotherapy for advanced renal cell carcinoma: evidence for the polyclonality of metastases. Cancer1981; 47: 1984. Google Scholar 16 : Clonal analysis of lymphocytes from tumor, peripheral blood, and nontumorous kidney in primary renal cell carcinoma. Cancer Res1990; 50: 2363. Google Scholar 17 : Autologous tumor-specific cytotoxicity of tumor-infiltrating lymphocytes derived from human renal cell carcinoma. J Immunother1991; 10: 347. Google Scholar 18 : Renal cell carcinoma-specific lysis by cytotoxic T-lymphocyte clones isolated from peripheral blood lymphocytes and tumor-infiltrating lymphocytes. Int J Cancer1996; 68: 177. Google Scholar 19 : Tumors-specific lysis of human renal cell carcinomas by tumor-infiltrting lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines. J Immunol1993; 151: 4209. Google Scholar 20 : Antitumor effects of α-interferon on a murine renal cancer (Renca) in vitro and in vivo. Cancer Res1990; 50: 5414. Google Scholar 21 : Urologic Cancer. Blackwell Sciences1997; . Google Scholar 22 : Renal cell carcinoma treated by vaccines fo active specific immunotherapy: correlation of survival with skin testing by autologous tumor cells. Cancer Immunol Immunother1990; 32: 62. Google Scholar 23 : Adjuvant immunotherapy treatment of renal carcinoma patients with autologous tumor cells and bacillus Calmette-Guerin. Cancer1996; 77: 2560. Google Scholar 24 : Human leukocyte antigen expression in renal cell carcinoma lesions does not predict the response to interferon therapy. J Immunother1992; 12: 64. Google Scholar From the Uro-Oncology Program, Norris Cotton Cancer Center, the Section of Urology, Department of Surgery, the Departments of Microbiology, Pathology, Radiology and Community and Family Medicine, and the Section of Hematology/Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire© 2000 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited bySCHWAAB T, TRETTER C, GIBSON J, COLE B, SCHNED A, HARRIS R, WALLEN E, FISHER J, WAUGH M, TRUMAN D, STEMPKOWSKI L, CROSBY N, HEANEY J and ERNSTOFF M (2018) Immunological Effects of Granulocyte-Macrophage Colony-Stimulating Factor and Autologous Tumor Vaccine in Patients With Renal Cell CarcinomaJournal of Urology, VOL. 171, NO. 3, (1036-1042), Online publication date: 1-Mar-2004. Volume 163Issue 4April 2000Page: 1322-1327 Advertisement Copyright & Permissions© 2000 by American Urological Association, Inc.Keywordsrenal cell cancerimmune regulationinterferonautologous vaccineMetricsAuthor Information THOMAS SCHWAAB More articles by this author JOHN A. HEANEY More articles by this author ALAN R. SCHNED More articles by this author ROBERT D. HARRIS More articles by this author BERNARD F. COLE More articles by this author RANDOLPH J. NOELLE More articles by this author DOROTHY M. PHILLIPS More articles by this author LAURA STEMPKOWSKI More articles by this author MARC S. ERNSTOFF More articles by this author Expand All Advertisement PDF downloadLoading ...