Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection

Improving Antibody Therapeutics by Manipulating the Fc Domain: Immunological and Structural Considerations

(2022) George Delidakis et al.   Annual Review of Biomedical Engineering

Predicting and Preventing Immune Checkpoint Inhibitor Toxicity: Targeting Cytokines

(2021) Jee Hye Kang et al.   TRENDS IN IMMUNOLOGY

Modeling cell-specific dynamics and regulation of the common gamma chain cytokines

(2021) Ali M. Farhat et al.   Cell Reports

Calibration of cell-intrinsic interleukin-2 response thresholds guides design of a regulatory T cell biased agonist

(2021) Caleb R Glassman et al.   eLife

Mouse IL-2/CD25 Fusion Protein Induces Regulatory T Cell Expansion and Immune Suppression in Preclinical Models of Systemic Lupus Erythematosus

(2021) Jenny H. Xie et al.   JOURNAL OF IMMUNOLOGY

The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes

(2021) Shen Dong et al.   JCI Insight

A general model of multivalent binding with ligands of heterotypic subunits and multiple surface receptors

(2021) Zhixin Cyrillus Tan et al.   MATHEMATICAL BIOSCIENCES

Engineered antibody fusion proteins for targeted disease therapy

(2021) Aliyah B. Silver et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Site-specific PEGylation of interleukin-2 enhances immunosuppression via the sustained activation of regulatory T cells

(2021) Bo Zhang et al.   Nature Biomedical Engineering

Rationale for IL-15 superagonists in cancer immunotherapy

(2020) Karin M. Knudson et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Interleukin-2 druggability is modulated by global conformational transitions controlled by a helical capping switch

(2020) Viviane S. De Paula et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy

(2020) Jared E Lopes et al.   Journal for ImmunoTherapy of Cancer

Autoimmune Endocrinopathies: An Emerging Complication of Immune Checkpoint Inhibitors

(2020) Zoe Quandt et al.   Annual Review of Medicine

Sustained IL-2R signaling of limited duration by high-dose mIL-2/mCD25 fusion protein amplifies tumor-reactive CD8+ T cells to enhance antitumor immunity

(2020) Rosmely Hernandez et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

Persistent IL-2 Receptor Signaling by IL-2/CD25 Fusion Protein Controls Diabetes in NOD Mice by Multiple Mechanisms

(2020) Natasha C. Ward et al.   DIABETES

A novel format for recombinant antibody-interleukin-2 fusion proteins exhibits superior tumor-targeting properties in vivo

(2020) Tiziano Ongaro et al.   Oncotarget

An IL-2 mutein engineered to promote expansion of regulatory T cells arrests ongoing autoimmunity in mice

(2020) Liliane Khoryati et al.   Science Immunology

Cytocidal macrophages in symbiosis with CD4 and CD8 T cells cause acute diabetes following checkpoint blockade of PD-1 in NOD mice

(2020) Hao Hu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Receptor-gated IL-2 delivery by an anti-human IL-2 antibody activates regulatory T cells in three different species

(2020) Ufuk Karakus et al.   Science Translational Medicine

An IL-2-grafted antibody immunotherapy with potent efficacy against metastatic cancer

(2020) Dilara Sahin et al.   Nature Communications

Targeted Delivery of IL2 to the Tumor Stroma Potentiates the Action of Immune Checkpoint Inhibitors by Preferential Activation of NK and CD8+ T Cells

(2019) Cornelia Hutmacher et al.   Cancer Immunology Research

An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes

(2019) Kevan C. Herold et al.   NEW ENGLAND JOURNAL OF MEDICINE

Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life

(2019) Kevin O. Saunders   Frontiers in Immunology

TCB2, a new anti-human interleukin-2 antibody, facilitates heterodimeric IL-2 receptor signaling and improves anti-tumor immunity

(2019) Jun-Young Lee et al.   OncoImmunology

First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation

(2018) Rizwan Romee et al.   BLOOD

Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors

(2018) Angeliki M. Stamatouli et al.   DIABETES

Blocking IL-2 Signal In Vivo with an IL-2 Antagonist Reduces Tumor Growth through the Control of Regulatory T Cells

(2018) Tania Carmenate et al.   JOURNAL OF IMMUNOLOGY

ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial

(2018) John M Wrangle et al.   LANCET ONCOLOGY

A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism

(2018) Eleonora Trotta et al.   NATURE MEDICINE

Engineering a Single-Agent Cytokine/Antibody Fusion That Selectively Expands Regulatory T Cells for Autoimmune Disease Therapy

(2018) Jamie B. Spangler et al.   JOURNAL OF IMMUNOLOGY

IL-2–Anti–IL-2 Monoclonal Antibody Immune Complexes Inhibit Collagen-Induced Arthritis by Augmenting Regulatory T Cell Functions

(2018) Yuichi Yokoyama et al.   JOURNAL OF IMMUNOLOGY

A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease

(2018) Laurence B. Peterson et al.   JOURNAL OF AUTOIMMUNITY

IL-2/CD25: A Long-Acting Fusion Protein That Promotes Immune Tolerance by Selectively Targeting the IL-2 Receptor on Regulatory T Cells

(2018) Natasha C. Ward et al.   JOURNAL OF IMMUNOLOGY

The Balancing Act between Cancer Immunity and Autoimmunity in Response to Immunotherapy

(2018) Arabella Young et al.   Cancer Immunology Research

Anti-cancer Therapies Employing IL-2 Cytokine Tumor Targeting: Contribution of Innate, Adaptive and Immunosuppressive Cells in the Anti-tumor Efficacy

(2018) Lorenzo Mortara et al.   Frontiers in Immunology

Is autoimmunity the Achilles' heel of cancer immunotherapy?

(2017) Carl H June et al.   NATURE MEDICINE

IgG Fc engineering to modulate antibody effector functions

(2017) Xinhua Wang et al.   Protein & Cell

Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental animal models of arthritis: a systematic literature review and meta-analysis

(2016) J S Dekkers et al.   ANNALS OF THE RHEUMATIC DISEASES

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma

(2016) Ajjai Alva et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models

(2016) D. H. Charych et al.   CLINICAL CANCER RESEARCH

Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2

(2016) N. Arenas-Ramirez et al.   Science Translational Medicine

Insights into Cytokine–Receptor Interactions from Cytokine Engineering

(2015) Jamie B. Spangler et al.   Annual Review of Immunology

Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms

(2015) Jamie B. Spangler et al.   IMMUNITY

The IL-2 cytokine family in cancer immunotherapy

(2014) Geok Choo Sim et al.   CYTOKINE & GROWTH FACTOR REVIEWS

IL-2: The First Effective Immunotherapy for Human Cancer

(2014) S. A. Rosenberg   JOURNAL OF IMMUNOLOGY

Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally

(2013) Jakub Tomala et al.   ACS Chemical Biology

Efficacy and Mechanism-of-Action of a Novel Superagonist Interleukin-15: Interleukin-15 Receptor  Su/Fc Fusion Complex in Syngeneic Murine Models of Multiple Myeloma

(2013) W. Xu et al.   CANCER RESEARCH

Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy

(2013) Wei Liao et al.   IMMUNITY

The Toxoplasma gondii Peptide AS15 Elicits CD4 T Cells That Can Control Parasite Burden

(2012) Harshita Satija Grover et al.   INFECTION AND IMMUNITY

Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+T reg cells

(2012) Jonathan M. Weiss et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo

(2012) Mahesh Yadav et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Competition for IL-2 between Regulatory and Effector T Cells to Chisel Immune Responses

(2012) Thomas Höfer et al.   Frontiers in Immunology

Molecular Mechanisms of Treg-Mediated T Cell Suppression

(2012) Angelika Schmidt et al.   Frontiers in Immunology

Interleukin-2 and Regulatory T Cells in Graft-versus-Host Disease

(2011) John Koreth et al.   NEW ENGLAND JOURNAL OF MEDICINE

Cellular Requirements for Diabetes Induction in DO11.10xRIPmOVA Mice

(2010) J. D. Wesley et al.   JOURNAL OF IMMUNOLOGY

Differential Regulation of Effector- and Central-Memory Responses to Toxoplasma gondii Infection by IL-12 Revealed by Tracking of Tgd057-Specific CD8+ T Cells

(2010) Douglas C. Wilson et al.   PLoS Pathogens

A Fusion Protein Composed of IL-2 and Caspase-3 Ameliorates the Outcome of Experimental Inflammatory Colitis

(2009) Yuval Sagiv et al.   Annals of the New York Academy of Sciences

Regulatory T Cells in the Control of Host-Microorganism Interactions

(2009) Yasmine Belkaid et al.   Annual Review of Immunology

Decrease of Foxp3+ Treg Cell Number and Acquisition of Effector Cell Phenotype during Lethal Infection

(2009) Guillaume Oldenhove et al.   IMMUNITY

In vivo expansion of T reg cells with IL-2–mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression

(2009) Kylie E. Webster et al.   JOURNAL OF EXPERIMENTAL MEDICINE

In Vivo Expansion of Activated Naive CD8+ T Cells and NK Cells Driven by Complexes of IL-2 and Anti-IL-2 Monoclonal Antibody As Novel Approach of Cancer Immunotherapy

(2009) J. Tomala et al.   JOURNAL OF IMMUNOLOGY

Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction

(2008) Qizhi Tang et al.   IMMUNITY

The Biology of Interleukin-2

(2007) Thomas R. Malek   Annual Review of Immunology