IL-2-driven CD8+ T cell phenotypes: implications for immunotherapy

Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8+ T cells and reprogramming macrophages

(2023) Mélanie Tichet et al.   IMMUNITY

Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2

(2023) Oksana Tsyklauri et al.   eLife

Simultaneous targeting of PD-1 and IL-2Rβγ with radiation therapy inhibits pancreatic cancer growth and metastasis

(2023) Miles Piper et al.   CANCER CELL

Bystander activation in memory and antigen-inexperienced memory-like CD8 T cells

(2023) Darina Paprckova et al.   CURRENT OPINION IN IMMUNOLOGY

Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8+ T cells

(2023) Jesus Corria-Osorio et al.   NATURE IMMUNOLOGY

Research progress of interleukin-15 in cancer immunotherapy

(2023) Menghan Cai et al.   Frontiers in Pharmacology

Robust IL-2-dependent antitumor immunotherapy requires targeting the high-affinity IL-2R on tumor-specific CD8+T cells

(2023) Kathryn M LaPorte et al.   Journal for ImmunoTherapy of Cancer

A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases

(2023) Miro E. Raeber et al.   EBioMedicine

Neoantigen-specific stem cell memory-like CD4+ T cells mediate CD8+ T cell-dependent immunotherapy of MHC class II-negative solid tumors

(2023) Spencer E. Brightman et al.   NATURE IMMUNOLOGY

Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments

(2022) Shogo Kumagai et al.   CANCER CELL

Fine-tuned long-acting interleukin-2 superkine potentiates durable immune responses in mice and non-human primate

(2022) Rosemina Merchant et al.   Journal for ImmunoTherapy of Cancer

TransCon IL-2 β/γ: a novel long-acting prodrug with sustained release of an IL-2Rβ/γ-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer

(2022) David B Rosen et al.   Journal for ImmunoTherapy of Cancer

PD-1-cis IL-2R agonism yields better effectors from stem-like CD8+ T cells

(2022) Laura Codarri Deak et al.   NATURE

PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program

(2022) Masao Hashimoto et al.   NATURE

A split, conditionally active mimetic of IL-2 reduces the toxicity of systemic cytokine therapy

(2022) Alfredo Quijano-Rubio et al.   NATURE BIOTECHNOLOGY

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

(2022) Derek VanDyke et al.   Cell Reports

IL-2-based Approaches to Treg Enhancement

(2022) Ffion Harris et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Interleukin-2–based therapies in cancer

(2022) Miro E. Raeber et al.   Science Translational Medicine

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein

(2022) Silvia Gaggero et al.   Science Immunology

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

(2021) Caleb R Glassman et al.   eLife

Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma

(2021) Adi Diab et al.   JOURNAL OF CLINICAL ONCOLOGY

Pharmacokinetics and Pharmacodynamic Effects of Nemvaleukin Alfa, a Selective Agonist of the Intermediate-Affinity IL-2 Receptor, in Cynomolgus Monkeys

(2021) Jared E. Lopes et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

An engineered IL-2 reprogrammed for anti-tumor therapy using a semi-synthetic organism

(2021) Jerod L. Ptacin et al.   Nature Communications

An Engineered IL15 Cytokine Mutein Fused to an Anti-PD1 Improves Intratumoral T-cell Function and Antitumor Immunity

(2021) Yuanming Xu et al.   Cancer Immunology Research

The role of CD4 T cells in rejection of solid tumors

(2021) Lucia Poncette et al.   CURRENT OPINION IN IMMUNOLOGY

An orthogonal IL-2 and IL-2Rβ system drives persistence and activation of CAR T cells and clearance of bulky lymphoma

(2021) Paul-Joseph Aspuria et al.   Science Translational Medicine

A human orthogonal IL-2 and IL-2Rβ system enhances CAR T cell expansion and antitumor activity in a murine model of leukemia

(2021) Qian Zhang et al.   Science Translational Medicine

Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy

(2020) Meenu Sharma et al.   Nature Communications

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

Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a Phase I/II randomised, double-blind, placebo-controlled, dose-finding study

(2020) Michelle Rosenzwajg et al.   DIABETOLOGIA

PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance

(2020) Catherine L. Tan et al.   JOURNAL OF EXPERIMENTAL MEDICINE

The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies

(2020) Shogo Kumagai et al.   NATURE IMMUNOLOGY

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

(2020) Dilara Sahin et al.   Nature Communications

De novo design of potent and selective mimics of IL-2 and IL-15

(2019) Daniel-Adriano Silva et al.   NATURE

PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer

(2019) Takahiro Kamada et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Memory CD4 T cell-derived IL-2 synergizes with viral infection to exacerbate lung inflammation

(2019) K. Kai McKinstry et al.   PLoS Pathogens

Effective Targeting of Multiple B-Cell Maturation Antigen–Expressing Hematological Malignances by Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor T Cells

(2018) Kevin M. Friedman et al.   HUMAN GENE THERAPY

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

(2018) Eleonora Trotta et al.   NATURE MEDICINE

Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes

(2018) Jonathan T. Sockolosky et al.   SCIENCE

S100 Proteins As an Important Regulator of Macrophage Inflammation

(2018) Chang Xia et al.   Frontiers in Immunology

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

A novel human IL-2 mutein with minimal systemic toxicity exerts greater antitumor efficacy than wild-type IL-2

(2018) Xi Chen et al.   Cell Death & Disease

Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial

(2018) Michelle Rosenzwajg et al.   ANNALS OF THE RHEUMATIC DISEASES

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

IL-2 Modulates the TCR Signaling Threshold for CD8 but Not CD4 T Cell Proliferation on a Single-Cell Level

(2017) Byron B. Au-Yeung et al.   JOURNAL OF IMMUNOLOGY

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

Interleukin 2 Activates Brain Microvascular Endothelial Cells Resulting in Destabilization of Adherens Junctions

(2016) Lukasz S. Wylezinski et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

An essential role for the IL-2 receptor in Treg cell function

(2016) Takatoshi Chinen et al.   NATURE IMMUNOLOGY

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

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

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

(2015) Jamie B. Spangler et al.   IMMUNITY

IL-2/anti-IL-2 mAb immunocomplexes: A renascence of IL-2 in cancer immunotherapy?

(2015) Jakub Tomala et al.   OncoImmunology

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

Human IL-2 Mutein with Higher Antitumor Efficacy Than Wild Type IL-2

(2013) T. Carmenate et al.   JOURNAL OF IMMUNOLOGY

Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’

(2012) Aron M. Levin et al.   NATURE

Molecular Mechanisms of Treg-Mediated T Cell Suppression

(2012) Angelika Schmidt et al.   Frontiers in Immunology

Regulatory T Cells Selectively Control CD8+ T Cell Effector Pool Size via IL-2 Restriction

(2011) W. Kastenmuller et al.   JOURNAL OF IMMUNOLOGY

CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis

(2011) A. McNally et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Interleukin-2 Receptor Signaling: At the Interface between Tolerance and Immunity

(2010) Thomas R. Malek et al.   IMMUNITY

IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor   subunit CD25

(2010) S. Letourneau et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells

(2010) C. Krieg et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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