gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.
Douglas J. Schwartzentruber,David H. Lawson,Jon M. Richards,Robert M. Conry,Donald M. Miller,Jonathan S. Treisman,Fawaz Gailani,Lee B. Riley,Kevin C. Conlon,Barbara A. Pockaj,Kari Kendra,Richard L. White,Rene Gonzalez,Timothy M. Kuzel,Brendan D. Curti,Phillip D. Leming,Eric D. Whitman,Jai Balkissoon,Douglas S. Reintgen,Howard L. Kaufman,Francesco M. Marincola,Maria J. Merino,Steven A. Rosenberg,Peter L. Choyke,Don Vena,Patrick Hwu +25 more
TLDR
In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine andInterleukin-2 than with interleuk in-2 alone.Abstract:
Background Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. Methods We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end p...read more
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Cancer immunotherapy comes of age
TL;DR: In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.
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Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future
Lieping Chen,Xue Han +1 more
TL;DR: This Review will focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity.
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Cancer Cell Membrane-Coated Nanoparticles for Anticancer Vaccination and Drug Delivery
Ronnie H. Fang,Che Ming Jack Hu,Brian T. Luk,Weiwei Gao,Jonathan Copp,Yiyin Tai,Derek E. O'Connor,Liangfang Zhang +7 more
TL;DR: The biological functionalization of polymeric nanoparticles with a layer of membrane coating derived from cancer cells is reported on, showing that by coupling the particles with an immunological adjuvant, the resulting formulation can be used to promote a tumor-specific immune response for use in vaccine applications.
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A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization
Miguel F. Sanmamed,Lieping Chen +1 more
TL;DR: The principles of immune normalization are highlighted and lessons learned are learned to guide better designs for future cancer immunotherapies.
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Cancer immunotherapy: the beginning of the end of cancer?
Sofia Farkona,Sofia Farkona,Eleftherios P. Diamandis,Eleftherios P. Diamandis,Eleftherios P. Diamandis,Ivan M. Blasutig,Ivan M. Blasutig,Ivan M. Blasutig +7 more
TL;DR: Some of the main strategies in cancer immunotherapy (cancer vaccines, adoptive cellular immunotherapy, immune checkpoint blockade, and oncolytic viruses) are outlined and the progress in the synergistic design of immune-targeting combination therapies is discussed.
References
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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
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Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
Philip W. Kantoff,Celestia S. Higano,N. Shore,E. Roy Berger,Eric J. Small,David F. Penson,Charles H. Redfern,Anna C. Ferrari,Robert Dreicer,Robert B. Sims,Yi Xu,Mark W. Frohlich,Paul F. Schellhammer +12 more
TL;DR: The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer and immune responses to the immunizing antigen were observed in patients who received sipuleUcel- T.
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Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma
Steven A. Rosenberg,James Chih-Hsin Yang,Douglas J. Schwartzentruber,Patrick Hwu,Francesco M. Marincola,Suzanne L. Topalian,Nicholas P. Restifo,Mark E. Dudley,Susan L. Schwarz,Paul J. Spiess,John R. Wunderlich,Maria R. Parkhurst,Yutaka Kawakami,Claudia A. Seipp,Jan Einhorn,Donald E. White +15 more
TL;DR: A synthetic peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma and, on the basis of immunologic assays, 91% of patients could be successfully immunized with this peptide.
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High-Dose Recombinant Interleukin 2 Therapy for Patients With Metastatic Melanoma: Analysis of 270 Patients Treated Between 1985 and 1993
Michael B. Atkins,Michael T. Lotze,Janice P. Dutcher,Richard I. Fisher,Geoffrey R. Weiss,Kim Margolin,Jeff Abrams,M. Sznol,David Parkinson,Michael Hawkins,Carolyn Paradise,Lori Kunkel,Steven A. Rosenberg +12 more
TL;DR: High-dose IL-2 treatment seems to benefit some patients with metastatic melanoma by producing durable CRs or PRs and should be considered for appropriately selected melanoma patients.
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Autoimmunity Correlates With Tumor Regression in Patients With Metastatic Melanoma Treated With Anti–Cytotoxic T-Lymphocyte Antigen-4
Peter Attia,Giao Q. Phan,Ajay V. Maker,Michael R. Robinson,Martha Quezado,James Chih-Hsin Yang,Richard M. Sherry,Suzanne L. Topalian,Udai S. Kammula,Richard E. Royal,Nicholas P. Restifo,Leah R. Haworth,Catherine Levy,Sharon Mavroukakis,Geoff M. Nichol,Michael Yellin,Steven A. Rosenberg +16 more
TL;DR: Administration of anti-CTLA-4 monoclonal antibody plus peptide vaccination can cause durable objective responses, which correlate with the induction of autoimmunity, in patients with metastatic melanoma.
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