Concepts for agonistic targeting of CD40 in immuno-oncology

First-in-human study with intratumoral administration of a CD40 agonistic antibody, ADC-1013, in advanced solid malignancies

(2019) Sandra M. M. Irenaeus et al.   INTERNATIONAL JOURNAL OF CANCER

IL-6 Signaling Blockade during CD40-Mediated Immune Activation Favors Antitumor Factors by Reducing TGF-β, Collagen Type I, and PD-L1/PD-1

(2019) Emma Eriksson et al.   JOURNAL OF IMMUNOLOGY

A CD40 agonist and PD-1 antagonist antibody reprogram the microenvironment of non-immunogenic tumors to allow T cell-mediated anticancer activity

(2019) Hayley S. Ma et al.   Cancer Immunology Research

Anti-PD-L1 treatment results in functional remodeling of the macrophage compartment

(2019) Huizhong Xiong et al.   CANCER RESEARCH

CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response

(2019) Nicholas F. Kuhn et al.   CANCER CELL

A tetravalent single chain diabody (CD40/HER2) efficiently inhibits tumor proliferation through recruitment of T cells and anti-HER2 functions

(2019) Li Lu et al.   MOLECULAR IMMUNOLOGY

Differential Effects of Depleting versus Programming Tumor-Associated Macrophages on Engineered T Cells in Pancreatic Ductal Adenocarcinoma

(2019) Ingunn M. Stromnes et al.   Cancer Immunology Research

Targeted APC Activation in Cancer Immunotherapy to Enhance the Abscopal Effect

(2019) Nathan Suek et al.   Frontiers in Immunology

HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of FcγR-binding functionality

(2019) David M. Richards et al.   Journal for ImmunoTherapy of Cancer

CD40L and TNF both activate the classical NF-κB pathway, which is not required for the CD40L induced alternative pathway in endothelial cells

(2018) J. Seigner et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

The Immune Revolution: A Case for Priming, Not Checkpoint

(2018) Robert H. Vonderheide   CANCER CELL

Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies

(2018) Xiaojie Yu et al.   CANCER CELL

Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors

(2018) Lindsay K. Ward-Kavanagh et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

Radiotherapy and CD40 activation separately augment immunity to checkpoint blockade in cancer

(2018) Andrew J Rech et al.   CANCER RESEARCH

Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity

(2018) Sabine Hoves et al.   JOURNAL OF EXPERIMENTAL MEDICINE

The promise and challenges of immune agonist antibody development in cancer

(2018) Patrick A. Mayes et al.   NATURE REVIEWS DRUG DISCOVERY

Gene therapy comes of age

(2018) Cynthia E. Dunbar et al.   SCIENCE

Macrophages and CD8 + T Cells Mediate the Antitumor Efficacy of Combined CD40 Ligation and Imatinib Therapy in Gastrointestinal Stromal Tumors

(2018) Jennifer Q. Zhang et al.   Cancer Immunology Research

Duokines: a novel class of dual-acting co-stimulatory molecules acting in cis or trans

(2018) Sina Fellermeier-Kopf et al.   OncoImmunology

Membrane-Bound CD40L Promotes Senescence and Initiates Senescence-Associated Secretory Phenotype via NF-κB Activation in Lung Adenocarcinoma

(2018) Wei Xu et al.   CELLULAR PHYSIOLOGY AND BIOCHEMISTRY

Improving Efficacy and Safety of Agonistic Anti-CD40 Antibody Through Extracellular Matrix Affinity

(2018) Jun Ishihara et al.   MOLECULAR CANCER THERAPEUTICS

Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer

(2018) Sayeda Yasmin-Karim et al.   Frontiers in Immunology

Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma

(2018) David L. Bajor et al.   OncoImmunology

A Single-Chain-Based Hexavalent CD27 Agonist Enhances T Cell Activation and Induces Anti-Tumor Immunity

(2018) Meinolf Thiemann et al.   Frontiers in Oncology

Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy

(2018) Laura A. Vitale et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

A tetrameric form of CD40 ligand with potent biological activities in both mouse and human primary B cells

(2018) Nannan Lai et al.   MOLECULAR IMMUNOLOGY

Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity

(2018) David A. Knorr et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Safety and Activity of Varlilumab, a Novel and First-in-Class Agonist Anti-CD27 Antibody, in Patients With Advanced Solid Tumors

(2017) Howard A. Burris et al.   JOURNAL OF CLINICAL ONCOLOGY

Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients

(2017) A. Schiza et al.   Journal of Translational Medicine

Macrophages as Key Drivers of Cancer Progression and Metastasis

(2017) Sebastian R. Nielsen et al.   MEDIATORS OF INFLAMMATION

Intratumoral CD40 activation and checkpoint blockade induces T cell-mediated eradication of melanoma in the brain

(2017) Manisha Singh et al.   Nature Communications

Local irradiation does not enhance the effect of immunostimulatory AdCD40L gene therapy combined with low dose cyclophosphamide in melanoma patients

(2017) Sandra Irenaeus et al.   Oncotarget

Combination of CD40 Agonism and CSF-1R Blockade Reconditions Tumor-Associated Macrophages and Drives Potent Antitumor Immunity

(2017) Karla R. Wiehagen et al.   Cancer Immunology Research

Intravenously usable fully serotype 3 oncolytic adenovirus coding for CD40L as an enabler of dendritic cell therapy

(2017) Sadia Zafar et al.   OncoImmunology

Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype

(2017) Nina Xue et al.   Scientific Reports

Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcγR Engagement

(2016) Rony Dahan et al.   CANCER CELL

Agonistic CD40 mAb-Driven IL12 Reverses Resistance to Anti-PD1 in a T-cell–Rich Tumor

(2016) Shin Foong Ngiow et al.   CANCER RESEARCH

Cancer immunotherapy: activating innate and adaptive immunity through CD40 agonists

(2016) Gregory L. Beatty et al.   Expert Review of Anticancer Therapy

CSF-1R–Dependent Lethal Hepatotoxicity When Agonistic CD40 Antibody Is Given before but Not after Chemotherapy

(2016) Katelyn T. Byrne et al.   JOURNAL OF IMMUNOLOGY

Functional Antagonism of Human CD40 Achieved by Targeting a Unique Species-Specific Epitope

(2016) Aaron P. Yamniuk et al.   JOURNAL OF MOLECULAR BIOLOGY

Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy

(2016) Kristin L. Griffiths et al.   Nature Communications

Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model

(2016) Nadia M. Luheshi et al.   Oncotarget

CD40-activated B cells induce anti-tumor immunity in vivo

(2016) Kerstin Wennhold et al.   Oncotarget

CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in Cancer

(2016) Katelyn T. Byrne et al.   Cell Reports

Principles of antibody-mediated TNF receptor activation

(2015) H Wajant   CELL DEATH AND DIFFERENTIATION

Vaccination Produces CD4 T Cells with a Novel CD154–CD40-Dependent Cytolytic Mechanism

(2015) Rhea N. Coler et al.   JOURNAL OF IMMUNOLOGY

Induction of an Altered CD40 Signaling Complex by an Antagonistic Human Monoclonal Antibody to CD40

(2015) Katherine C. Bankert et al.   JOURNAL OF IMMUNOLOGY

Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms

(2015) Tamás Rőszer   MEDIATORS OF INFLAMMATION

CD40/CD40L expression correlates with the survival of patients with glioblastomas and an augmentation in CD40 signaling enhances the efficacy of vaccinations against glioma models

(2015) Masashi Chonan et al.   NEURO-ONCOLOGY

Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage

(2015) José Medina-Echeverz et al.   Cancer Immunology Research

Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation

(2014) Menno C. van Zelm et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

OK432-Activated Human Dendritic Cells Kill Tumor Cells via CD40/CD40 Ligand Interactions

(2014) K. S. Hill et al.   JOURNAL OF IMMUNOLOGY

T Cell–B Cell Thymic Cross-Talk: Maintenance and Function of Thymic B Cells Requires Cognate CD40–CD40 Ligand Interaction

(2014) Chiharu Fujihara et al.   JOURNAL OF IMMUNOLOGY

An optimized Protocol for Human M2 Macrophages using M-CSF and IL-4/IL-10/TGF-βYields a Dominant Immunosuppressive Phenotype

(2014) S. Mia et al.   SCANDINAVIAN JOURNAL OF IMMUNOLOGY

Multifunctional CD40L: pro- and anti-neoplastic activity

(2014) Aleksandra Korniluk et al.   TUMOR BIOLOGY

Myeloid Colony-Stimulating Factors as Regulators of Macrophage Polarization

(2014) Thomas A. Hamilton et al.   Frontiers in Immunology

Understanding the influence of the tumor microenvironment on macrophage responses to CD40 agonists

(2014) Nadia Luheshi et al.   OncoImmunology

Agonistic CD40 Antibodies and Cancer Therapy

(2013) R. H. Vonderheide et al.   CLINICAL CANCER RESEARCH

Th1 cytokines are more effective than Th2 cytokines at licensing anti-tumour functions in CD40-activated human macrophages in vitro

(2013) Nadia Luheshi et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Antitumor effects of anti-CD40/CpG immunotherapy combined with gemcitabine or 5-fluorouracil chemotherapy in the B16 melanoma model

(2013) Xiaoyi Qu et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

APG350 Induces Superior Clustering of TRAIL Receptors and Shows Therapeutic Antitumor Efficacy Independent of Cross-Linking via Fc  Receptors

(2013) C. Gieffers et al.   MOLECULAR CANCER THERAPEUTICS

Agonistic Antibody to CD40 Boosts the Antitumor Activity of Adoptively Transferred T Cells In Vivo

(2012) Chengwen Liu et al.   JOURNAL OF IMMUNOTHERAPY

Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia

(2012) John C. Byrd et al.   LEUKEMIA & LYMPHOMA

CD40-Activated B Cells Can Efficiently Prime Antigen-Specific Naïve CD8+ T Cells to Generate Effector but Not Memory T cells

(2012) Mélissa Mathieu et al.   PLoS One

The Fas/CD95 Receptor Regulates the Death of Autoreactive B Cells and the Selection of Antigen-Specific B Cells

(2012) Gabor Koncz et al.   Frontiers in Immunology

Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2-non-amplified breast cancer cell lines

(2011) D. M. Collins et al.   ANNALS OF ONCOLOGY

Local Activation of CD8 T Cells and Systemic Tumor Eradication without Toxicity via Slow Release and Local Delivery of Agonistic CD40 Antibody

(2011) M. F. Fransen et al.   CLINICAL CANCER RESEARCH

Rapid onset of ICAM-1 expression is a marker of effective macrophages activation during infection of Francisella tularensis LVS in vitro

(2011) J. Novosad et al.   FOLIA MICROBIOLOGICA

Crystallographic and Mutational Analysis of the CD40-CD154 Complex and Its Implications for Receptor Activation

(2011) Hyun-Jung An et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

M2 Macrophages Induced by Prostaglandin E2 and IL-6 from Cervical Carcinoma Are Switched to Activated M1 Macrophages by CD4+ Th1 Cells

(2011) M. Heusinkveld et al.   JOURNAL OF IMMUNOLOGY

Inhibitory Fc  Receptor Engagement Drives Adjuvant and Anti-Tumor Activities of Agonistic CD40 Antibodies

(2011) F. Li et al.   SCIENCE

Adenoviral vaccination combined with CD40 stimulation and CTLA-4 blockage can lead to complete tumor regression in a murine melanoma model

(2010) Maria R. Sorensen et al.   VACCINE

Molecular mechanism and function of CD40/CD40L engagement in the immune system

(2009) Raul Elgueta et al.   IMMUNOLOGICAL REVIEWS

Trimer Stabilization, Oligomerization, and Antibody-Mediated Cell Surface Immobilization Improve the Activity of Soluble Trimers of CD27L, CD40L, 41BBL, and Glucocorticoid-Induced TNF Receptor Ligand

(2009) A. Wyzgol et al.   JOURNAL OF IMMUNOLOGY

Generation of Human CD40-activated B cells

(2009) Tanja M. Liebig et al.   Jove-Journal of Visualized Experiments

CD40-activated B cells can be generated in high number and purity in cancer patients: analysis of immunogenicity and homing potential

(2008) E. Kondo et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY