PURPOSE: The objective of this study was to determine the tolerance and effect of moderate-dose recombinant human interleukin-2 (rHu IL-2) and tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) refractory to standard therapy. PATIENTS AND METHODS: Twenty-six patients (18 MM and eight RCC) were entered onto this pilot study. TIL were isolated from fresh biopsy material and activated with anti-CD3 antibody, OKT3, for 48 hours and expanded in 100 IU/mL r-methionyl Hu IL-2 alanine 125 (r-met Hu IL-2 [ala-125]). At least 10(10) TIL were reinfused intravenously in three divided injections on days 2, 4, and 6 of the protocol. A maximum dose of 30,000 U/kg of IL-2 per injection was administered every 8 hours from day 2 through day 11 for a total of 28 doses. RESULTS: Sixteen melanoma patients completed the study. Of these, three (19%) showed a durable complete response (CR), nine (56%) had no response (NR), and four (25%) had progressive disease (PD). One nonresponder demonstrated complete tumor regression within 1 year of treatment. Of four assessable RCC patients, two experienced a minor response (MR) and two showed NR. All TIL cultures showed comparably high cytotoxic activity as determined by antibody-redirected lysis (ARL). More importantly, melanoma TIL from responders possessed significantly higher cytotoxicity against autologous tumor cells than TIL from nonresponders (P < .05). Production of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-4 was similar for TIL from melanoma responders and nonresponders, or TIL from RCC patients. CONCLUSIONS: Immunotherapy with polyclonally activated TIL and moderate-dose IL-2 could be successfully used for the treatment of immunogenic tumors with less toxicity and lower costs as compared with high-dose IL-2 protocols.
PURPOSE: The objective of this study was to determine the tolerance and effect of moderate-dose recombinant humaninterleukin-2 (rHu IL-2) and tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) refractory to standard therapy. PATIENTS AND METHODS: Twenty-six patients (18 MM and eight RCC) were entered onto this pilot study. TIL were isolated from fresh biopsy material and activated with anti-CD3 antibody, OKT3, for 48 hours and expanded in 100 IU/mL r-methionyl Hu IL-2alanine 125 (r-met Hu IL-2 [ala-125]). At least 10(10) TIL were reinfused intravenously in three divided injections on days 2, 4, and 6 of the protocol. A maximum dose of 30,000 U/kg of IL-2 per injection was administered every 8 hours from day 2 through day 11 for a total of 28 doses. RESULTS: Sixteen melanomapatients completed the study. Of these, three (19%) showed a durable complete response (CR), nine (56%) had no response (NR), and four (25%) had progressive disease (PD). One nonresponder demonstrated complete tumor regression within 1 year of treatment. Of four assessable RCCpatients, two experienced a minor response (MR) and two showed NR. All TIL cultures showed comparably high cytotoxic activity as determined by antibody-redirected lysis (ARL). More importantly, melanoma TIL from responders possessed significantly higher cytotoxicity against autologous tumor cells than TIL from nonresponders (P < .05). Production of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-4 was similar for TIL from melanoma responders and nonresponders, or TIL from RCCpatients. CONCLUSIONS: Immunotherapy with polyclonally activated TIL and moderate-dose IL-2 could be successfully used for the treatment of immunogenic tumors with less toxicity and lower costs as compared with high-dose IL-2 protocols.
Authors: Egbert Oosterwijk; W Kimryn Rathmell; Kerstin Junker; A Rose Brannon; Frédéric Pouliot; David S Finley; Peter F A Mulders; Ziya Kirkali; Hirotsugo Uemura; Arie Belldegrun Journal: Eur Urol Date: 2011-07-05 Impact factor: 20.096
Authors: Linh T Nguyen; Pei Hua Yen; Jessica Nie; Nicole Liadis; Danny Ghazarian; Ayman Al-Habeeb; Alexandra Easson; Wey Leong; Joan Lipa; David McCready; Michael Reedijk; David Hogg; Anthony M Joshua; Ian Quirt; Hans Messner; Patricia Shaw; Michael Crump; Eran Sharon; Pamela S Ohashi Journal: PLoS One Date: 2010-11-10 Impact factor: 3.240
Authors: Thomas Schwaab; Adrian Schwarzer; Benita Wolf; Todd S Crocenzi; John D Seigne; Nancy A Crosby; Bernard F Cole; Jan L Fisher; Jill C Uhlenhake; Diane Mellinger; Cathy Foster; Zbigniew M Szczepiorkowski; Susan M Webber; Alan R Schned; Robert D Harris; Richard J Barth; John A Heaney; Randolph J Noelle; Marc S Ernstoff Journal: Clin Cancer Res Date: 2009-07-21 Impact factor: 12.531
Authors: Brian A Rabinovich; Yang Ye; Tamara Etto; Jie Qing Chen; Hyam I Levitsky; Willem W Overwijk; Laurence J N Cooper; Juri Gelovani; Patrick Hwu Journal: Proc Natl Acad Sci U S A Date: 2008-09-15 Impact factor: 11.205
Authors: R K Alpaugh; M von Mehren; I Palazzo; M B Atkins; J A Sparano; L Schuchter; L M Weiner; J P Dutcher Journal: Med Oncol Date: 1998-09 Impact factor: 3.064