A bispecific antibody agonist of the IL-2 heterodimeric receptor preferentially promotes in vivo expansion of CD8 and NK cells

[1]  F. Janku,et al.  Preliminary results from an open-label, multicenter phase 1/2 dose escalation and expansion study of THOR-707, a novel not-Alpha IL-2, as a single agent in adult subjects with advanced or metastatic solid tumors , 2020 .

[2]  H. Hirte,et al.  1027MO ALKS 4230 monotherapy and in combination with pembrolizumab (pembro) in patients (pts) with refractory solid tumours (ARTISTRY-1) , 2020 .

[3]  S. Gettinger,et al.  Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02). , 2020, Cancer discovery.

[4]  J. Fisher,et al.  ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy , 2020, Journal for ImmunoTherapy of Cancer.

[5]  J. Safrit,et al.  The human IL-15 superagonist N-803 promotes migration of virus-specific CD8+ T and NK cells to B cell follicles but does not reverse latency in ART-suppressed, SHIV-infected macaques , 2020, PLoS pathogens.

[6]  D. Neri,et al.  Antibody-cytokine fusion proteins: A novel class of biopharmaceuticals for the therapy of cancer and of chronic inflammation. , 2019, New biotechnology.

[7]  E. L. Potter,et al.  IL15 by Continuous Intravenous Infusion to Adult Patients with Solid Tumors in a Phase I Trial Induced Dramatic NK-Cell Subset Expansion , 2019, Clinical Cancer Research.

[8]  Michael J. Osborn,et al.  Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies , 2019, Front. Immunol..

[9]  Brian D. Weitzner,et al.  De novo design of potent and selective mimics of IL-2 and IL-15 , 2019, Nature.

[10]  J. Desjarlais,et al.  Abstract 5565: Potency-reduced IL15/IL15Rα heterodimeric Fc-fusions display enhanced in vivo activity through increased exposure , 2018, Clinical Research (Excluding Clinical Trials).

[11]  T. Nayak,et al.  89Zr-labeled CEA-targeted IL-2 variant immunocytokine in patients with solid tumors: CEA-mediated tumor accumulation and role of IL-2 receptor-binding , 2018, Oncotarget.

[12]  Wei Wu,et al.  Prospects of IL-2 in Cancer Immunotherapy , 2018, BioMed research international.

[13]  Michael J. Osborn,et al.  Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies , 2018, Front. Immunol..

[14]  C. Klein,et al.  Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines , 2017, Oncoimmunology.

[15]  B. Brannetti,et al.  Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2 , 2016, Science Translational Medicine.

[16]  M. Addepalli,et al.  NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models , 2016, Clinical Cancer Research.

[17]  O. Boyman,et al.  Interleukin-2: Biology, Design and Application. , 2015, Trends in immunology.

[18]  T. Anchordoquy,et al.  Potential induction of anti-PEG antibodies and complement activation toward PEGylated therapeutics. , 2014, Drug discovery today.

[19]  L. Radvanyi,et al.  The IL-2 cytokine family in cancer immunotherapy. , 2014, Cytokine & growth factor reviews.

[20]  S. Rosenberg.  IL-2: The First Effective Immunotherapy for Human Cancer , 2014, The Journal of Immunology.

[21]  R. Lufkin,et al.  Durable responses and reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cancer in a Community Hospital Biotherapy Program , 2014, Journal of Immunotherapy for Cancer.

[22]  P. Hwu,et al.  IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients. , 2014, The Journal of clinical investigation.

[23]  Claudia C. Preston,et al.  The Ratios of CD8+ T Cells to CD4+CD25+ FOXP3+ and FOXP3- T Cells Correlate with Poor Clinical Outcome in Human Serous Ovarian Cancer , 2013, PloS one.

[24]  J. Wolchok,et al.  Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma , 2013, The Journal of experimental medicine.

[25]  H. Wong,et al.  Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor αSu/Fc fusion complex in syngeneic murine models of multiple myeloma. , 2013, Cancer research.

[26]  J. Sims,et al.  A whole blood in vitro cytokine release assay with aqueous monoclonal antibody presentation for the prediction of therapeutic protein induced cytokine release syndrome in humans. , 2012, Cytokine.

[27]  W. Klapper,et al.  Targeting Interleukin-2 to the Neovasculature Potentiates Rituximab‘s Activity Against Mantle Cell Lymphoma in Mice , 2012 .

[28]  Vijay S. Pande,et al.  Exploiting a natural conformational switch to engineer an Interleukin-2 superkine , 2012, Nature.

[29]  J. Sprent,et al.  The role of interleukin-2 during homeostasis and activation of the immune system , 2012, Nature Reviews Immunology.

[30]  F. Carrat,et al.  Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. , 2011, The New England journal of medicine.

[31]  J. Ritz,et al.  Interleukin-2 and regulatory T cells in graft-versus-host disease. , 2011, The New England journal of medicine.

[32]  F. Marincola,et al.  gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. , 2011, The New England journal of medicine.

[33]  Saileta Prabhu,et al.  Projecting human pharmacokinetics of therapeutic antibodies from nonclinical data , 2011, mAbs.

[34]  Michael W. Sneddon,et al.  Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response , 2010, Molecular systems biology.

[35]  F. D. De Braud,et al.  The tumour-targeting human L19-IL2 immunocytokine: preclinical safety studies, phase I clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma. , 2010, European journal of cancer.

[36]  G. Pantaleo,et al.  Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells , 2010, Proceedings of the National Academy of Sciences.

[37]  W. Klapper,et al.  Complete eradication of human B-cell lymphoma xenografts using rituximab in combination with the immunocytokine L19-IL2. , 2009, Blood.

[38]  Anne S De Groot,et al.  Immunogenicity of protein therapeutics. , 2007, Trends in immunology.

[39]  T. Waldmann.  IL-15 in the life and death of lymphocytes: Implications for cancer therapy and vaccine design , 2007 .

[40]  K. Rezvani,et al.  High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. , 2006, Blood.

[41]  T. Waldmann.  The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design , 2006, Nature Reviews Immunology.

[42]  A. Rudensky,et al.  A function for interleukin 2 in Foxp3-expressing regulatory T cells , 2005, Nature Immunology.

[43]  K. Christopher Garcia,et al.  The Structure of Interleukin-2 Complexed with Its Alpha Receptor , 2005, Science.

[44]  P. Parren,et al.  In vitro characterization of five humanized OKT3 effector function variant antibodies. , 2000, Cellular immunology.

[45]  M. Doyle,et al.  Elimination of Fc Receptor-Dependent Effector Functions of a Modified IgG4 Monoclonal Antibody to Human CD4 , 2000, The Journal of Immunology.

[46]  R. Fisher,et al.  High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  S. Steinberg,et al.  Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. , 1998, Annals of surgery.

[48]  Camellia W. Adams,et al.  An efficient route to human bispecific IgG , 1998, Nature Biotechnology.

[49]  M. Madanat,et al.  Intrachain disulfide bond in the core hinge region of human IgG4 , 1997, Protein science : a publication of the Protein Society.

[50]  L. Presta,et al.  'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. , 1996, Protein engineering.

[51]  T. Loughran,et al.  Establishment of an IL‐2 independent, human T‐cell line possessing only the p70 IL‐2 receptor , 1991, International journal of cancer.

[52]  S. Morrison,et al.  The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region , 1991, The Journal of experimental medicine.

[53]  S. Rosenberg,et al.  In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. , 1985, Journal of immunology.

[54]  V. Velcheti,et al.  PHASE I TRIAL OF ALT-803, A NOVEL RECOMBINANT INTERLEUKIN-15 COMPLEX, IN PATIENTS WITH ADVANCED SOLID TUMORS , 2018 .

[55]  D. Pardoll,et al.  Therapeutic administration of IL‐15 superagonist complex ALT‐803 leads to long‐term survival and durable antitumor immune response in a murine glioblastoma model , 2016, International journal of cancer.

[56]  T. Waldmann,et al.  Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[57]  M. Atkins,et al.  Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.