Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways

ARC-8: Phase I/Ib study to evaluate safety and tolerability of AB680 + chemotherapy + zimberelimab (AB122) in patients with treatment-naive metastatic pancreatic adenocarcinoma (mPDAC).

(2021) Gulam Abbas Manji et al.   JOURNAL OF CLINICAL ONCOLOGY

Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion

(2021) Nicole E. Scharping et al.   NATURE IMMUNOLOGY

CTLA-4 blockade drives loss of Treg stability in glycolysis-low tumours

(2021) Roberta Zappasodi et al.   NATURE

Metabolic support of tumour-infiltrating regulatory T cells by lactic acid

(2021) McLane J. Watson et al.   NATURE

Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells

(2021) Rebekka Duhen et al.   Nature Communications

Analysis of OX40 agonist antibody (PF-04518600) in patients with hepatocellular carcinoma.

(2020) Anthony B. El-Khoueiry et al.   JOURNAL OF CLINICAL ONCOLOGY

FS222, a CD137/PD-L1 tetravalent bispecific antibody exhibits low toxicity and anti-tumor activity in colorectal cancer models

(2020) Matthew A Lakins et al.   CLINICAL CANCER RESEARCH

Obesity and CD8 T cell metabolism: Implications for anti‐tumor immunity and cancer immunotherapy outcomes

(2020) William J. Turbitt et al.   IMMUNOLOGICAL REVIEWS

Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE).

(2020) Delvys Rodriguez-Abreu et al.   JOURNAL OF CLINICAL ONCOLOGY

Initial results from a phase II study (TACTI-002) in metastatic non-small cell lung or head and neck carcinoma patients receiving eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab.

(2020) Enriqueta Felip et al.   JOURNAL OF CLINICAL ONCOLOGY

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

(2020) Zhilin Zou et al.   Cell and Bioscience

Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence

(2020) Raju K. Vaddepally et al.   Cancers

Focusing on Adenosine Receptors as a Potential Targeted Therapy in Human Diseases

(2020) Wiwin Is Effendi et al.   Cells

Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives

(2020) Mark R. Middleton et al.   BRITISH JOURNAL OF CANCER

Metabolic signaling in T cells

(2020) Justin A. Shyer et al.   CELL RESEARCH

Low-Dose Metformin Reprograms the Tumor Immune Microenvironment in Human Esophageal Cancer: Results of a Phase II Clinical Trial

(2020) Shuhong Wang et al.   CLINICAL CANCER RESEARCH

Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen

(2020) Santosha A. Vardhana et al.   NATURE IMMUNOLOGY

The adenosine pathway in immuno-oncology

(2020) Bertrand Allard et al.   Nature Reviews Clinical Oncology

Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding

(2020) Lawrence P. Andrews et al.   Science Immunology

LBA48 Clinical efficacy and immunity of combination therapy with nivolumab and IDO/PD-L1 peptide vaccine in patients with metastatic melanoma: A phase I/II trial

(2020) I-M. Svane et al.   ANNALS OF ONCOLOGY

1400P Vibostolimab, an anti-TIGIT antibody, as monotherapy and in combination with pembrolizumab in anti-PD-1/PD-L1-refractory NSCLC

(2020) M-J. Ahn et al.   ANNALS OF ONCOLOGY

First‐in‐human phase 1 study of MK‐1248, an anti–glucocorticoid‐induced tumor necrosis factor receptor agonist monoclonal antibody, as monotherapy or with pembrolizumab in patients with advanced solid tumors

(2020) Ravit Geva et al.   CANCER

Safety and Clinical Activity of MEDI1873, a Novel GITR Agonist, in Advanced Solid Tumors

(2020) Ani S. Balmanoukian et al.   CLINICAL CANCER RESEARCH

An antibody targeting ICOS increases intratumoral cytotoxic to regulatory T cell ratio and induces tumor regression

(2020) Richard C.A. Sainson et al.   Cancer Immunology Research

LAG-3: from molecular functions to clinical applications

(2020) Takumi Maruhashi et al.   Journal for ImmunoTherapy of Cancer

Rational design of anti-GITR-based combination immunotherapy

(2019) Roberta Zappasodi et al.   NATURE MEDICINE

The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation

(2019) Anne Månsson Kvarnhammar et al.   Journal for ImmunoTherapy of Cancer

Characterization and comparison of GITR expression in solid tumors

(2019) Luis Vence et al.   CLINICAL CANCER RESEARCH

4‐1BB Delineates Distinct Activation Status of Exhausted Tumor‐Infiltrating CD8 + T cells in Hepatocellular Carcinoma

(2019) Hyung‐Don Kim et al.   HEPATOLOGY

In situ vaccination with defined factors overcomes T cell exhaustion in distant tumors

(2019) Danny N. Khalil et al.   JOURNAL OF CLINICAL INVESTIGATION

Immune checkpoints in the tumor microenvironment

(2019) Salman M. Toor et al.   SEMINARS IN CANCER BIOLOGY

OX40 Agonist Tumor Immunotherapy Does Not Impact Regulatory T Cell Suppressive Function

(2019) Fanny Polesso et al.   JOURNAL OF IMMUNOLOGY

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study

(2019) Georgina V Long et al.   LANCET ONCOLOGY

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

(2019) James Larkin et al.   NEW ENGLAND JOURNAL OF MEDICINE

1119PDInducible T cell costimulatory (ICOS) receptor agonist, GSK3359609 (GSK609) alone and in combination with pembrolizumab (pembro): Preliminary results from INDUCE-1 expansion cohorts (EC) in head and neck squamous cell carcinoma (HNSCC)

(2019) D Rischin et al.   ANNALS OF ONCOLOGY

Metabolic Consequences of T-cell Costimulation in Anticancer Immunity

(2019) Alvaro Teijeira et al.   Cancer Immunology Research

Safety, Tolerability, and Potential Clinical Activity of a Glucocorticoid-Induced TNF Receptor–Related Protein Agonist Alone or in Combination With Nivolumab for Patients With Advanced Solid Tumors

(2019) Kimberley M. Heinhuis et al.   JAMA Oncology

Reprogramming of fatty acid metabolism in cancer

(2019) Nikos Koundouros et al.   BRITISH JOURNAL OF CANCER

TIGIT as an emerging immune checkpoint

(2019) H. Harjunpää et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

A phase Ib study of utomilumab (PF-05082566) in combination with mogamulizumab in patients with advanced solid tumors

(2019) Ezra E. W. Cohen et al.   Journal for ImmunoTherapy of Cancer

Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer

(2018) Lifeng Li et al.   CANCER RESEARCH

Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer

(2018) Neil H. Segal et al.   CLINICAL CANCER RESEARCH

Regulation of the Immune Response by the Aryl Hydrocarbon Receptor

(2018) Cristina Gutiérrez-Vázquez et al.   IMMUNITY

Next generation of immune checkpoint therapy in cancer: new developments and challenges

(2018) Julian A. Marin-Acevedo et al.   Journal of Hematology & Oncology

Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity

(2018) Qing Zhang et al.   NATURE IMMUNOLOGY

Safety of combining radiotherapy with immune-checkpoint inhibition

(2018) William L. Hwang et al.   Nature Reviews Clinical Oncology

The promise and challenges of immune agonist antibody development in cancer

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

Prostate cancer: Enhancing VTP

(2018) Clemens Thoma   Nature Reviews Urology

Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

(2018) Michael A. Postow et al.   NEW ENGLAND JOURNAL OF MEDICINE

A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted Therapy in Advanced Melanoma

(2018) Lukas Krähenbühl et al.   NEOPLASIA

A Landscape of Metabolic Variation across Tumor Types

(2018) Ed Reznik et al.   Cell Systems

Targeting adenosine for cancer immunotherapy

(2018) Robert D. Leone et al.   Journal for ImmunoTherapy of Cancer

ICONIC: Biologic and clinical activity of first in class ICOS agonist antibody JTX-2011 +/- nivolumab (nivo) in patients (pts) with advanced cancers.

(2018) Timothy Anthony Yap et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase I/II study of LAG525 ± spartalizumab (PDR001) in patients (pts) with advanced malignancies.

(2018) David S. Hong et al.   JOURNAL OF CLINICAL ONCOLOGY

First-in-human phase 1 study of MK-1248, an anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody, as monotherapy or in combination with pembrolizumab in patients with advanced solid tumors.

(2018) Ravit Geva et al.   JOURNAL OF CLINICAL ONCOLOGY

Dose escalation results from a first-in-human, phase 1 study of glucocorticoid-induced TNF receptor–related protein agonist AMG 228 in patients with advanced solid tumors

(2018) Ben Tran et al.   Journal for ImmunoTherapy of Cancer

Putting the Immunologic Brakes on Cancer

(2018) Jedd Wolchok   CELL

Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3

(2018) Jun Wang et al.   CELL

Tim-3 expression and its role in hepatocellular carcinoma

(2018) Feifei Liu et al.   Journal of Hematology & Oncology

Tim-3 and its role in regulating anti-tumor immunity

(2017) Madhumita Das et al.   IMMUNOLOGICAL REVIEWS

LAG3 (CD223) as a cancer immunotherapy target

(2017) Lawrence P. Andrews et al.   IMMUNOLOGICAL REVIEWS

The future of immune checkpoint cancer therapy after PD-1 and CTLA-4

(2017) Andrew W Hahn et al.   Immunotherapy

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

(2017) Jedd D. Wolchok et al.   NEW ENGLAND JOURNAL OF MEDICINE

TIGIT: A Key Inhibitor of the Cancer Immunity Cycle

(2017) Nicholas A. Manieri et al.   TRENDS IN IMMUNOLOGY

CTLA-4 and PD-1 Pathways

(2016) Elizabeth I. Buchbinder et al.   AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS

Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis

(2016) C. Coyle et al.   ANNALS OF ONCOLOGY

Rationale for anti-GITR cancer immunotherapy

(2016) Deborah A. Knee et al.   EUROPEAN JOURNAL OF CANCER

Emerging concepts of T cell metabolism as a target of immunotherapy

(2016) Chih-Hao Chang et al.   NATURE IMMUNOLOGY

Pathological  -synuclein transmission initiated by binding lymphocyte-activation gene 3

(2016) X. Mao et al.   SCIENCE

Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia

(2016) Nicole E. Scharping et al.   Cancer Immunology Research

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

(2015) Robert H.I. Andtbacka et al.   JOURNAL OF CLINICAL ONCOLOGY

Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma

(2015) Dirk Schadendorf et al.   JOURNAL OF CLINICAL ONCOLOGY

Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity

(2015) Stefani Spranger et al.   NATURE

Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma

(2015) Michael A. Postow et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer

(2015) N. A. Rizvi et al.   SCIENCE

Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells

(2015) T. Kouo et al.   Cancer Immunology Research

LSECtin Expressed on Melanoma Cells Promotes Tumor Progression by Inhibiting Antitumor T-cell Responses

(2014) F. Xu et al.   CANCER RESEARCH

CEACAM1 regulates TIM-3-mediated tolerance and exhaustion

(2014) Yu-Hwa Huang et al.   NATURE

An endogenous aryl hydrocarbon receptor ligand inhibits proliferation and migration of human ovarian cancer cells

(2013) Kai Wang et al.   CANCER LETTERS

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

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

AhR expression is increased in hepatocellular carcinoma

(2013) Ziyu Liu et al.   JOURNAL OF MOLECULAR HISTOLOGY

Cancer Immunotherapy

(2013) J. Couzin-Frankel   SCIENCE

Tolerance and exhaustion: defining mechanisms of T cell dysfunction

(2013) Andrea Schietinger et al.   TRENDS IN IMMUNOLOGY

GITR Pathway Activation Abrogates Tumor Immune Suppression through Loss of Regulatory T-cell Lineage Stability

(2013) D. A. Schaer et al.   Cancer Immunology Research

The TIGIT/CD226 Axis Regulates Human T Cell Function

(2012) E. Lozano et al.   JOURNAL OF IMMUNOLOGY

Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma

(2012) Michael A. Postow et al.   NEW ENGLAND JOURNAL OF MEDICINE

Potent Induction of Tumor Immunity by Combining Tumor Cryoablation with Anti-CTLA-4 Therapy

(2011) R. Waitz et al.   CANCER RESEARCH

Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape

(2011) S.-R. Woo et al.   CANCER RESEARCH

VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses

(2011) Li Wang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

T cell exhaustion

(2011) E John Wherry   NATURE IMMUNOLOGY

CD47-signal regulatory protein-  (SIRP ) interactions form a barrier for antibody-mediated tumor cell destruction

(2011) X. W. Zhao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Selective Depletion of CD4+CD25+Foxp3+Regulatory T Cells by Low-Dose Cyclophosphamide Is Explained by Reduced Intracellular ATP Levels

(2010) Jie Zhao et al.   CANCER RESEARCH

Ah receptor antagonism inhibits constitutive and cytokine inducible IL6 production in head and neck tumor cell lines

(2010) Brett C. DiNatale et al.   MOLECULAR CARCINOGENESIS

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

(2010) F. Stephen Hodi et al.   NEW ENGLAND JOURNAL OF MEDICINE

A Phase I Pharmacokinetic and Biological Correlative Study of IMP321, a Novel MHC Class II Agonist, in Patients with Advanced Renal Cell Carcinoma

(2009) C. Brignone et al.   CLINICAL CANCER RESEARCH

Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti-CTLA-4 Antibody

(2009) M. Z. Dewan et al.   CLINICAL CANCER RESEARCH

OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis

(2009) Daniel Hirschhorn-Cymerman et al.   JOURNAL OF EXPERIMENTAL MEDICINE

The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells

(2008) Xin Yu et al.   NATURE IMMUNOLOGY