4-1BB Agonists: Multi-Potent Potentiators of Tumor Immunity

Immune checkpoint combinations from mouse to man

(2015) Midan Ai et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

High expression of OX40 (CD134) and 4-1BB (CD137) molecules on CD4+CD25high cells in children with type 1 diabetes

(2014) Agnieszka Szypowska et al.   Advances in Medical Sciences

4-1BB Chimeric Antigen Receptors

(2014) Dario Campana et al.   CANCER JOURNAL

Agonistic anti-CD137 antibody treatment leads to antitumor response in mice with liver cancer

(2014) Vanessa Gauttier et al.   INTERNATIONAL JOURNAL OF CANCER

Targeting CD137 enhances the efficacy of cetuximab

(2014) Holbrook E. Kohrt et al.   JOURNAL OF CLINICAL INVESTIGATION

Galectin-9 controls the therapeutic activity of 4-1BB–targeting antibodies

(2014) Shravan Madireddi et al.   JOURNAL OF EXPERIMENTAL MEDICINE

ERK-Dependent Bim Modulation Downstream of the 4-1BB-TRAF1 Signaling Axis Is a Critical Mediator of CD8 T Cell Survival In Vivo

(2014) L. Sabbagh et al.   JOURNAL OF IMMUNOLOGY

4-1BB Engagement Costimulates NKT Cell Activation and Exacerbates NKT Cell Ligand-Induced Airway Hyperresponsiveness and Inflammation

(2014) D.-H. Kim et al.   JOURNAL OF IMMUNOLOGY

Self-Antigen Prevents CD8 T Cell Effector Differentiation by CD134 and CD137 Dual Costimulation

(2014) S. Bandyopadhyay et al.   JOURNAL OF IMMUNOLOGY

Endogenous 4-1BB Ligand Plays a Critical Role in Protection from Influenza-Induced Disease

(2014) G. H. Y. Lin et al.   JOURNAL OF IMMUNOLOGY

4-1BB-based Isolation and Expansion of CD8+ T Cells Specific for Self-Tumor and Non–Self-Tumor Antigens for Adoptive T-cell Therapy

(2014) Beom K. Choi et al.   JOURNAL OF IMMUNOTHERAPY

CD137-CD137L Interaction Regulates Atherosclerosis via Cyclophilin A in Apolipoprotein E-Deficient Mice

(2014) Yuefeng Li et al.   PLoS One

Focal Radiation Therapy Combined with 4-1BB Activation and CTLA-4 Blockade Yields Long-Term Survival and a Protective Antigen-Specific Memory Response in a Murine Glioma Model

(2014) Zineb Belcaid et al.   PLoS One

Targeting 4-1BB Costimulation to the Tumor Stroma with Bispecific Aptamer Conjugates Enhances the Therapeutic Index of Tumor Immunotherapy

(2014) B. Schrand et al.   Cancer Immunology Research

Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells in a Poorly Immunogenic Tumor Model

(2014) S. Chen et al.   Cancer Immunology Research

Eomesodermin is required for antitumor immunity mediated by 4-1BB-agonist immunotherapy

(2014) Chang Song et al.   OncoImmunology

TRAF1 phosphorylation on Serine 139 modulates NF-κB activity downstream of 4-1BB in T cells

(2013) N.A. Eustache Oussa et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Therapeutic PD-1 Pathway Blockade Augments with Other Modalities of Immunotherapy T-Cell Function to Prevent Immune Decline in Ovarian Cancer

(2013) J. Duraiswamy et al.   CANCER RESEARCH

The effect of CD137–CD137 ligand interaction on phospholipase C signaling pathway in human endothelial cells

(2013) Jinchuan Yan et al.   CHEMICO-BIOLOGICAL INTERACTIONS

Use of Oligonucleotide Aptamer Ligands to Modulate the Function of Immune Receptors

(2013) E. Gilboa et al.   CLINICAL CANCER RESEARCH

CD137 Accurately Identifies and Enriches for Naturally Occurring Tumor-Reactive T Cells in Tumor

(2013) Q. Ye et al.   CLINICAL CANCER RESEARCH

Immunomodulatory Monoclonal Antibodies Combined with Peptide Vaccination Provide Potent Immunotherapy in an Aggressive Murine Neuroblastoma Model

(2013) E. L. Williams et al.   CLINICAL CANCER RESEARCH

The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy

(2013) Amy E Moran et al.   CURRENT OPINION IN IMMUNOLOGY

4-1BB signal stimulates the activation, expansion, and effector functions of γδ T cells in mice and humans

(2013) Seung J. Lee et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

CD134/CD137 dual costimulation-elicited IFN-γ maximizes effector T-cell function but limits Treg expansion

(2013) Marie-Clare St. Rose et al.   IMMUNOLOGY AND CELL BIOLOGY

Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity

(2013) Alexey Berezhnoy et al.   JOURNAL OF CLINICAL INVESTIGATION

Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin

(2013) Michael A. Curran et al.   JOURNAL OF EXPERIMENTAL MEDICINE

T Cell Costimulation with Anti-CD137 Monoclonal Antibodies Is Mediated by K63-Polyubiquitin-Dependent Signals from Endosomes

(2013) I. Martinez-Forero et al.   JOURNAL OF IMMUNOLOGY

GITR-Dependent Regulation of 4-1BB Expression: Implications for T Cell Memory and Anti-4-1BB-Induced Pathology

(2013) G. H. Y. Lin et al.   JOURNAL OF IMMUNOLOGY

Leukocyte-specific protein 1 links TNF receptor-associated factor 1 to survival signaling downstream of 4-1BB in T cells

(2013) Laurent Sabbagh et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Combined TIM-3 blockade and CD137 activation affords the long-term protection in a murine model of ovarian cancer

(2013) Zhiqiang Guo et al.   Journal of Translational Medicine

Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation

(2013) Ngoc Hoan Le et al.   MEDIATORS OF INFLAMMATION

Clinical targeting of the TNF and TNFR superfamilies

(2013) Michael Croft et al.   NATURE REVIEWS DRUG DISCOVERY

CD137 Facilitates the Resolution of Acute DSS-Induced Colonic Inflammation in Mice

(2013) Julia M. Martínez Gómez et al.   PLoS One

4-1BB Signaling Activates the T Cell Factor 1 Effector/β-Catenin Pathway with Delayed Kinetics via ERK Signaling and Delayed PI3K/AKT Activation to Promote the Proliferation of CD8+ T Cells

(2013) Do Y. Lee et al.   PLoS One

Combinatorial PD-1 Blockade and CD137 Activation Has Therapeutic Efficacy in Murine Cancer Models and Synergizes with Cisplatin

(2013) Huafeng Wei et al.   PLoS One

Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index

(2013) L. R. Desnoyers et al.   Science Translational Medicine

Gene Silencing of 4-1BB by RNA Interference Inhibits Acute Rejection in Rats with Liver Transplantation

(2013) Yang Shi et al.   Biomed Research International

The TNF receptor-ligands 4-1BB-4-1BBL and GITR-GITRL in NK cell responses

(2013) Isabel Barao   Frontiers in Immunology

Ectopic CD137 expression facilitates the escape of Hodgkin and Reed-Sternberg cells from immunosurveillance

(2013) Wan Lu Pang et al.   OncoImmunology

Essential complicity of perforin-granzyme and FAS-L mechanisms to achieve tumor rejection following treatment with anti-CD137 mAb

(2013) Aizea Morales-Kastresana et al.   Journal for ImmunoTherapy of Cancer

CD137 Is Expressed in Follicular Dendritic Cell Tumors and in Classical Hodgkin and T-Cell Lymphomas

(2012) Matthew W. Anderson et al.   AMERICAN JOURNAL OF PATHOLOGY

CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results

(2012) B. G. Till et al.   BLOOD

Combined stimulation of TLR9 and 4.1BB augments Trp2 peptide vaccine-mediated melanoma rejection by increasing Ag-specific CTL activity and infiltration into tumor sites

(2012) Jeong-Im Sin et al.   CANCER LETTERS

Expression of CD137 on Hodgkin and Reed-Sternberg Cells Inhibits T-cell Activation by Eliminating CD137 Ligand Expression

(2012) W. T. Ho et al.   CANCER RESEARCH

Oncolytic Virus and Anti-4-1BB Combination Therapy Elicits Strong Antitumor Immunity against Established Cancer

(2012) L. B. John et al.   CANCER RESEARCH

Adoptive Cell Therapy for Lymphoma with CD4 T Cells Depleted of CD137-Expressing Regulatory T Cells

(2012) M. J. Goldstein et al.   CANCER RESEARCH

Combination Immunotherapy with 4-1BBL and CTLA-4 Blockade for the Treatment of Prostate Cancer

(2012) Kuang Youlin et al.   Clinical & Developmental Immunology

CD137 on inflamed lymphatic endothelial cells enhances CCL21-guided migration of dendritic cells

(2012) Álvaro Teijeira et al.   FASEB JOURNAL

Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer

(2012) Holbrook E. Kohrt et al.   JOURNAL OF CLINICAL INVESTIGATION

Cutting Edge: 4-1BB Controls Regulatory Activity in Dendritic Cells through Promoting Optimal Expression of Retinal Dehydrogenase

(2012) S.-W. Lee et al.   JOURNAL OF IMMUNOLOGY

A Converse 4-1BB and CD40 Ligand Expression Pattern Delineates Activated Regulatory T Cells (Treg) and Conventional T Cells Enabling Direct Isolation of Alloantigen-Reactive Natural Foxp3+ Treg

(2012) A. Schoenbrunn et al.   JOURNAL OF IMMUNOLOGY

4-1BB/4-1BBL Interaction Promotes Obesity-Induced Adipose Inflammation by Triggering Bidirectional Inflammatory Signaling in Adipocytes/Macrophages

(2012) Thai Hien Tu et al.   MEDIATORS OF INFLAMMATION

Immunotherapeutic Synergy Between Anti-CD137 mAb and Intratumoral Administration of a Cytopathic Semliki Forest Virus Encoding IL-12

(2012) José I Quetglas et al.   MOLECULAR THERAPY

Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

(2012) Julie R. Brahmer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer

(2012) Suzanne L. Topalian et al.   NEW ENGLAND JOURNAL OF MEDICINE

SA-4-1BBL Costimulation Inhibits Conversion of Conventional CD4+ T Cells into CD4+FoxP3+ T Regulatory Cells by Production of IFN-γ

(2012) Shravan Madireddi et al.   PLoS One

4-1BB Signaling Breaks the Tolerance of Maternal CD8+ T Cells That Are Reactive with Alloantigens

(2012) Kwang H. Kim et al.   PLoS One

Prime-Boost Vaccination with SA-4-1BBL Costimulatory Molecule and Survivin Eradicates Lung Carcinoma in CD8+ T and NK Cell Dependent Manner

(2012) Abhishek K. Srivastava et al.   PLoS One

Exposure of a Distinct PDCA-1+ (CD317) B Cell Population to Agonistic Anti-4-1BB (CD137) Inhibits T and B Cell Responses Both In Vitro and In Vivo

(2012) Dass S. Vinay et al.   PLoS One

The HIF-1α Hypoxia Response in Tumor-Infiltrating T Lymphocytes Induces Functional CD137 (4-1BB) for Immunotherapy

(2012) Asís Palazón et al.   Cancer Discovery

Targeting 4-1BB (CD137) to enhance CD8 T cell responses with poxviruses and viral antigens

(2012) Yuan Zhao et al.   Frontiers in Immunology

Virotherapy, gene transfer and immunostimulatory monoclonal antibodies

(2012) José I. Quetglas et al.   OncoImmunology

Agonist Anti-CD137 mAb Act on Tumor Endothelial Cells to Enhance Recruitment of Activated T Lymphocytes

(2011) A. Palazon et al.   CANCER RESEARCH

4-1BB signaling beyond T cells

(2011) Dass S Vinay et al.   Cellular & Molecular Immunology

Unified immune modulation by 4-1BB triggering leads to diverse effects on disease progression in vivo

(2011) Beom K. Choi et al.   CYTOKINE

Deficiency for Costimulatory Receptor 4-1BB Protects Against Obesity-Induced Inflammation and Metabolic Disorders

(2011) C.-S. Kim et al.   DIABETES

Dispensable role for 4-1BB and 4-1BBL in development of vaccinia virus-specific CD8 T cells

(2011) Yuan Zhao et al.   IMMUNOLOGY LETTERS

4-1BB Triggering Ameliorates Experimental Autoimmune Encephalomyelitis by Modulating the Balance between Th17 and Regulatory T Cells

(2011) Y. H. Kim et al.   JOURNAL OF IMMUNOLOGY

CD134 Plus CD137 Dual Costimulation Induces Eomesodermin in CD4 T Cells To Program Cytotoxic Th1 Differentiation

(2011) H. Z. Qui et al.   JOURNAL OF IMMUNOLOGY

Costimulation Through the CD137/4-1BB Pathway Protects Human Melanoma Tumor-infiltrating Lymphocytes From Activation-induced Cell Death and Enhances Antitumor Effector Function

(2011) Jessica Ann Hernandez-Chacon et al.   JOURNAL OF IMMUNOTHERAPY

The combination of 4-1BBL and CD40L strongly enhances the capacity of dendritic cells to stimulate HIV-specific T cell responses

(2011) Brenda De Keersmaecker et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Combinatorial Therapy for Liver Metastatic Colon Cancer: Dendritic Cell Vaccine and Low-Dose Agonistic Anti-4-1BB Antibody Co-Stimulatory Signal

(2011) Hyunah Lee et al.   JOURNAL OF SURGICAL RESEARCH

Targeting 4-1BB Costimulation to Disseminated Tumor Lesions With Bi-specific Oligonucleotide Aptamers

(2011) Fernando Pastor et al.   MOLECULAR THERAPY

Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production

(2011) Michael A. Curran et al.   PLoS One

Incorporation of 4-1BB ligand into an adenovirus vaccine vector increases the number of functional antigen-specific CD8 T cells and enhances the duration of protection against influenza-induced respiratory disease

(2011) Theo J. Moraes et al.   VACCINE

Effects of 4-1BB signaling on the biological function of murine dendritic cells

(2011) YOULIN KUANG et al.   Oncology Letters

CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies

(2010) H. E. Kohrt et al.   BLOOD

Human    T lymphocytes induce robust NK cell-mediated antitumor cytotoxicity through CD137 engagement

(2010) A. Maniar et al.   BLOOD

Anti-4-1BB scFv immunogene therapy and low dose cyclophosphamide exhibit a synergistic antitumor effect in established murine lung tumors

(2010) Fang Liu et al.   CANCER BIOLOGY & THERAPY

Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ

(2010) Juan Dubrot et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

4-1BB Ligand as an Effective Multifunctional Immunomodulator and Antigen Delivery Vehicle for the Development of Therapeutic Cancer Vaccines

(2010) R. K. Sharma et al.   CANCER RESEARCH

4-1BB (CD137) Ligand Enhanced Anti-Tumor Immune Response against Mouse Forestomach Carcinoma In Vivo

(2010) Qiaoxia Li et al.   Cellular & Molecular Immunology

CD137 (4–1BB) Deficiency Reduces Atherosclerosis in Hyperlipidemic Mice

(2010) Hyung Jun Jeon et al.   CIRCULATION

Biphasic role of 4-1BB in the regulation of mouse cytomegalovirus-specific CD8+ T cells

(2010) Ian R. Humphreys et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration

(2010) Young-Mi Kim et al.   EXPERIMENTAL AND MOLECULAR MEDICINE

Intratumoral injection of interferon-α and systemic delivery of agonist anti-CD137 monoclonal antibodies synergize for immunotherapy

(2010) Juan Dubrot et al.   INTERNATIONAL JOURNAL OF CANCER

Triple expression of B7-1, B7-2 and 4-1BBL enhanced antitumor immune response against mouse H22 hepatocellular carcinoma

(2010) Guoqiang Li et al.   JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

CD137-Mediated Pathogenesis from Chronic Hepatitis to Hepatocellular Carcinoma in Hepatitis B Virus-Transgenic Mice

(2010) J. Wang et al.   JOURNAL OF IMMUNOLOGY

Regulation of Granulocyte and Macrophage Populations of Murine Bone Marrow Cells by G-CSF and CD137 Protein

(2010) Dongsheng Jiang et al.   PLoS One

Radiotherapy Enhances Antitumor Effect of Anti-CD137 Therapy in a Mouse Glioma Model

(2010) Elizabeth W. Newcomb et al.   RADIATION RESEARCH

Clinical Experiences With Anti-CD137 and Anti-PD1 Therapeutic Antibodies

(2010) Paolo A. Ascierto et al.   SEMINARS IN ONCOLOGY

Ex vivo expansion of natural killer cells with high cytotoxicity by K562 cells modified to co-express major histocompatibility complex class I chain-related protein A, 4-1BB ligand, and interleukin-15

(2010) W. Gong et al.   TISSUE ANTIGENS

SA-4-1BBL as the immunomodulatory component of a HPV-16 E7 protein based vaccine shows robust therapeutic efficacy in a mouse cervical cancer model

(2010) Rajesh K. Sharma et al.   VACCINE

Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion

(2009) R. Houot et al.   BLOOD

Costimulation as a Platform for the Development of Vaccines: A Peptide-Based Vaccine Containing a Novel Form of 4-1BB Ligand Eradicates Established Tumors

(2009) R. K. Sharma et al.   CANCER RESEARCH

Host Lymphodepletion Enhances the Therapeutic Activity of an Oncolytic Vaccinia Virus Expressing 4-1BB Ligand

(2009) H. S. Kim et al.   CANCER RESEARCH

In vivo depletion of DC impairs the anti-tumor effect of agonistic anti-CD137 mAb

(2009) Oihana Murillo et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Stimulation of the Molecule 4-1BB Enhances Host Defense against Listeria monocytogenes Infection in Mice by Inducing Rapid Infiltration and Activation of Neutrophils and Monocytes

(2009) S.-C. Lee et al.   INFECTION AND IMMUNITY

CD137 Promotes Proliferation and Survival of Human B Cells

(2009) X. Zhang et al.   JOURNAL OF IMMUNOLOGY

Hypercostimulation through 4-1BB Distorts Homeostasis of Immune Cells

(2009) S.-W. Lee et al.   JOURNAL OF IMMUNOLOGY

4-1BB Functions As a Survival Factor in Dendritic Cells

(2009) B. K. Choi et al.   JOURNAL OF IMMUNOLOGY

IFN-γ-indoleamine-2,3 dioxygenase acts as a major suppressive factor in 4-1BB-mediated immune suppression in vivo

(2009) Young H. Kim et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Mechanisms involved in synergistic anticancer effects of anti-4-1BB and cyclophosphamide therapy

(2009) Y. H. Kim et al.   MOLECULAR CANCER THERAPEUTICS

Therapeutic and Tumor-specific Immunity Induced by Combination of Dendritic Cells and Oncolytic Adenovirus Expressing IL-12 and 4-1BBL

(2009) Jing-Hua Huang et al.   MOLECULAR THERAPY

A novel form of 4-1BBL has better immunomodulatory activity than an agonistic anti-4-1BB Ab without Ab-associated severe toxicity

(2009) Rich-Henry Schabowsky et al.   VACCINE

Fc-dependent expression of CD137 on human NK cells: insights into "agonistic" effects of anti-CD137 monoclonal antibodies

(2008) W. Lin et al.   BLOOD

Combination Therapy with Cisplatin and Anti-4-1BB: Synergistic Anticancer Effects and Amelioration of Cisplatin-Induced Nephrotoxicity

(2008) Y. H. Kim et al.   CANCER RESEARCH

Analysis of CD137 and CD137L Expression in Human Primary Tumor Tissues

(2008) Qun Wang et al.   CROATIAN MEDICAL JOURNAL

Immune regulation and control of regulatory T cells by OX40 and 4-1BB

(2008) Takanori So et al.   CYTOKINE & GROWTH FACTOR REVIEWS

The 4-1BB ligand and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling

(2008) Jihyun Yang et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Eradication of established renal cell carcinoma by a combination of 5-fluorouracil and anti-4-1BB monoclonal antibody in mice

(2008) Seong-A Ju et al.   INTERNATIONAL JOURNAL OF CANCER

Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice

(2008) James O. McNamara et al.   JOURNAL OF CLINICAL INVESTIGATION

Phase I/II Study of Ipilimumab for Patients With Metastatic Melanoma

(2008) Jeffrey S. Weber et al.   JOURNAL OF CLINICAL ONCOLOGY

Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells

(2008) Seung-Woo Lee et al.   NATURE IMMUNOLOGY

Overcoming Immunologic Tolerance to Melanoma: Targeting CTLA-4 with Ipilimumab (MDX-010)

(2008) J. Weber   ONCOLOGIST

The administration of IL-12/GM-CSF and Ig-4-1BB ligand markedly decreases murine floor of mouth squamous cell cancer

(2008) Nithin D. Adappa et al.   OTOLARYNGOLOGY-HEAD AND NECK SURGERY