Journal ArticleDOI
A phase II study of high-dose continuous infusion interleukin-2 with lymphokine-activated killer cells in patients with metastatic melanoma.
Janice P. Dutcher,E R Gaynor,D H Boldt,J H Doroshow,M H Bar,M Sznol,James W. Mier,Joseph A. Sparano,R I Fisher,Geoffrey R. Weiss +9 more
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TLDR
When comparing the IVCI schedule with high-dose bolus IL2 to LAK cells in nonrandomized but sequential studies in patients with advanced melanoma, it appears that CI IL2 is less efficacious.Abstract:
Thirty-three patients with metastatic melanoma were treated in a phase II study with an intravenous continuous infusion (IVCI) of interleukin-2 (IL2) given with lymphokine-activated killer (LAK) cells. The dose of IL2 was the optimal priming dose for LAK-cell induction, followed by the maximally tolerated LAK-cell dose that could be given by an IVCI schedule as determined by a previous phase I trial. The CI schedule was chosen for evaluation because of a postulated reduction in toxicity with the possibility of administering a more prolonged IL2 infusion and because greater rebound lymphocytosis and LAK-cell generation had been reported using this dose and schedule. The 33 patients were similar in age, performance status, and sites of disease to those treated in previous IL2 trials. All patients were assessable for response and toxicity. One patient (3%) achieved a partial response of 10 months duration. There were no other clinically significant responses. Significant toxicity included hypotension requiri...read more
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Vascular leak syndrome: a side effect of immunotherapy.
Roxana Baluna,Ellen S. Vitetta +1 more
TL;DR: The major dose-limiting toxicity of interleukin-2 (IL-2) and of immunotoxin (IT) therapies is vascular leak syndrome (VLS), characterized by an increase in vascular permeability accompanied by extravasation of fluids and proteins resulting in interstitial edema and organ failure.
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Immunotherapy and gene therapy of cancer.
TL;DR: These experimetnal cancer treatments deserve vigorous exploration and should be considered for further exploration.
Journal ArticleDOI
Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome
TL;DR: Evidence that a three amino acid sequence motif, (x)D(y), in toxins and IL-2 damages ECs is provided and it is suggested that deletions or mutations in this sequence or the use of nondamaging blocking peptides may increase the therapeutic index of bothIL-2, as well as ITs prepared with a variety of plant or bacterial toxins.
Journal ArticleDOI
Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer
Ruth Whittington,Diana Faulds +1 more
TL;DR: In conclusion, IL-2 offers hope to some patients with renal cell carcinoma, malignant melanoma and other neoplastic disease, but appropriate patient selection and optimum dosage regimens are at present unresolved.
Journal ArticleDOI
A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors
Salah Eddine Bentebibel,Michael E. Hurwitz,Chantale Bernatchez,Cara Haymaker,Courtney W. Hudgens,Harriet M. Kluger,Michael T. Tetzlaff,Mary Tagliaferri,Jonathan Zalevsky,Ute Hoch,Christie Fanton,Sandra Aung,Patrick Hwu,Brendan D. Curti,Nizar M. Tannir,Mario Sznol,Adi Diab +16 more
TL;DR: In this paper, NKTR-214 (bempegaldesleukin) is a novel IL2 pathway agonist, designed to provide sustained signaling through heterodimeric IL2 receptor βγ to drive increased proliferation and activation of CD8+ T and natural killer cells without unwanted expansion of T regulatory cells (Tregs) in the tumor microenvironment.
References
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Journal ArticleDOI
Biological activity of recombinant human interleukin-2 produced in Escherichia coli
Steven A. Rosenberg,Elizabeth A. Grimm,Michael Mcgrogan,Michael Doyle,Ernest S. Kawasaki,Kirston E. Koths,David F. Mark +6 more
TL;DR: The recombinant lymphokine supports the growth of murine and human interleukin-2 dependent cell lines, enhances the generation of cytolytic cells in vitro and in vivo after alloimmunization, and generates lymphokin activated killer cells from murineand human lymphocytes.
Journal ArticleDOI
Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines.
Kim Margolin,Anthony A. Rayner,Michael J. Hawkins,Michael B. Atkins,Janice P. Dutcher,Richard I. Fisher,Geoffrey R. Weiss,James H. Doroshow,H S Jaffe,M Roper +9 more
TL;DR: The National Cancer Institute Extramural IL2/LAK Working Group treated 93 patients with 114 cycles of high-dose intravenous interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells in three phase II trials, finding that the intensity of this regimen limits this approach to a subset of cancer patients with excellent performance status and adequate organ function.
Journal ArticleDOI
Effectiveness and tolerability of low-dose cyclophosphamide and low-dose intravenous interleukin-2 in disseminated melanoma [corrected].
Malcolm S. Mitchell,Raymond A. Kempf,William Harel,Hungyi Shau,William D. Boswell,Susan Lind,Edward C. Bradley +6 more
TL;DR: This regimen appeared to be as effective in melanoma as those involving ex vivo activation of LAK cells, and was generally tolerable to patients in all age groups.
Journal Article
Clinical and immunological effects of recombinant interleukin 2 given by repetitive weekly cycles to patients with cancer.
Paul M. Sondel,Peter C. Kohler,Jacquelyn A. Hank,Karen H. Moore,Rosenthal Ns,Jeffrey A. Sosman,Robin Bechhofer,Barry E. Storer +7 more
TL;DR: A relatively well tolerated immunotherapy regimen using IL-2 can induce dramatic increases in lymphocyte number and augment their in vitro antitumor reactivity.
Journal ArticleDOI
A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma.
Geoffrey R. Weiss,K A Margolin,Frederick R. Aronson,M Sznol,M B Atkins,J. P. Dutcher,E R Gaynor,David H. Boldt,J H Doroshow,M H Bar +9 more
TL;DR: A randomized phase II trial of two intravenous high-dose rIL-2 regimens to determine if either one manifests greater anticancer activity or a more acceptable toxicity profile in patients with metastatic renal cell carcinoma.