Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion

Cytotoxic effect of CLL‑1 CAR‑T cell immunotherapy with PD‑1 silencing on relapsed/refractory acute myeloid leukemia

(2021) Guoqiang Lin et al.   Molecular Medicine Reports

CAR T cells in solid tumors: challenges and opportunities

(2021) Faroogh Marofi et al.   Stem Cell Research & Therapy

Deletion of Cbl-b inhibits CD8+ T-cell exhaustion and promotes CAR T-cell function

(2021) Jitendra Kumar et al.   Journal for ImmunoTherapy of Cancer

Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections

(2021) Ekaterina Zmievskaya et al.   Biomedicines

Anti-CD19 CAR-T cell therapy bridge to HSCT decreases the relapse rate and improves the long-term survival of R/R B-ALL patients: a systematic review and meta-analysis

(2021) Linhui Hu et al.   ANNALS OF HEMATOLOGY

Transcriptional regulatory network for the establishment of CD8+ T cell exhaustion

(2021) Wooseok Seo et al.   EXPERIMENTAL AND MOLECULAR MEDICINE

Author Correction: Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia

(2021) Joseph A. Fraietta et al.   NATURE MEDICINE

T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors

(2021) Takayoshi Yamauchi et al.   Nature Communications

Synthetic promoters to induce immune-effectors into the tumor microenvironment

(2021) Yariv Greenshpan et al.   Communications Biology

Enhancing CAR-T cell efficacy in solid tumors by targeting the tumor microenvironment

(2021) Guangna Liu et al.   Cellular & Molecular Immunology

Self-driving armored CAR-T cells overcome suppressive milieu and eradicate CD19+ Raji lymphoma in preclinical models

(2021) Brian Webster et al.   MOLECULAR THERAPY

Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling

(2021) Evan W. Weber et al.   SCIENCE

CAR-T cell therapy: current limitations and potential strategies

(2021) Robert C. Sterner et al.   Blood Cancer Journal

Role of nuclear localization in the regulation and function of T-bet and Eomes in exhausted CD8 T cells

(2021) Laura M. McLane et al.   Cell Reports

TOX as a potential target for immunotherapy in lymphocytic malignancies

(2021) Chaofeng Liang et al.   Biomarker Research

Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors

(2021) Zhenguang Wang et al.   Cellular & Molecular Immunology

Transforming growth factor-β-regulated mTOR activity preserves cellular metabolism to maintain long-term T cell responses in chronic infection

(2021) Sarah S. Gabriel et al.   IMMUNITY

IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin

(2021) Nengzhi Pang et al.   Journal of Hematology & Oncology

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma

(2021) Xiaoqian Liu et al.   Translational Oncology

A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab

(2021) Prasad S Adusumilli et al.   Cancer Discovery

Secretion of bispecific protein of anti-PD-1 fused with TGF-β trap enhances antitumor efficacy of CAR-T cell therapy

(2021) Xianhui Chen et al.   Molecular Therapy-Oncolytics

GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity

(2021) Sabine Heitzeneder et al.   CANCER CELL

EGFRvIII-CAR-T Cells with PD-1 Knockout Have Improved Anti-Glioma Activity

(2020) Haifeng Zhu et al.   PATHOLOGY & ONCOLOGY RESEARCH

Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer

(2020) Kyungsoo Kim et al.   Genome Medicine

Emerging Approaches for Regulation and Control of CAR T Cells: A Mini Review

(2020) Lærke J. B. Brandt et al.   Frontiers in Immunology

Adoptive T-cell therapy for HBV-associated HCC and HBV infection

(2020) Anthony T. Tan et al.   ANTIVIRAL RESEARCH

Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms

(2020) Jean-Christophe Beltra et al.   IMMUNITY

Charting the Roadmap of T Cell Exhaustion

(2020) Talyn Chu et al.   IMMUNITY

Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy

(2020) Xiaodong Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

TGFβ suppresses CD8+ T cell expression of CXCR3 and tumor trafficking

(2020) Andrew J. Gunderson et al.   Nature Communications

The Role of PD-1 in Acute and Chronic Infection

(2020) Jil M. Jubel et al.   Frontiers in Immunology

Chimeric antigen receptor signaling: Functional consequences and design implications

(2020) S. E. Lindner et al.   Science Advances

Inhibition of TGF-β-receptor signaling augments the antitumor function of ROR1-specific CAR T-cells against triple-negative breast cancer

(2020) Tanja Stüber et al.   Journal for ImmunoTherapy of Cancer

TIGIT expression is associated with T-cell suppression and exhaustion and predicts clinical outcome and anti-PD-1 response in follicular lymphoma

(2020) Zhi-Zhang Yang et al.   CLINICAL CANCER RESEARCH

Transcriptome profiling identifies TIGIT as a marker of T cell exhaustion in liver cancer

(2020) Dmitrij Ostroumov et al.   HEPATOLOGY

Ligand-Induced Degradation of a CAR Permits Reversible Remote Control of CAR T Cell Activity In Vitro and In Vivo

(2020) Sarah A. Richman et al.   MOLECULAR THERAPY

A conformation-specific ON-switch for controlling CAR T cells with an orally available drug

(2020) Charlotte U. Zajc et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape

(2020) Alba Rodriguez-Garcia et al.   Frontiers in Immunology

Discovery of a novel selective water-soluble SMAD3 inhibitor as an antitumor agent

(2020) Nannan Wu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Arming Anti-EGFRvIII CAR-T With TGFβ Trap Improves Antitumor Efficacy in Glioma Mouse Models

(2020) You Li et al.   Frontiers in Oncology

PD-1 silencing improves anti-tumor activities of human mesothelin-targeted CAR T cells

(2020) Guodi Liu et al.   HUMAN IMMUNOLOGY

Adoptive cell therapy: Living drugs against cancer

(2020) Tamara Laskowski et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Counteracting CAR T cell dysfunction

(2020) Mansour Poorebrahim et al.   ONCOGENE

Challenges and Opportunities of Using Adoptive T-Cell Therapy as Part of an HIV Cure Strategy

(2020) Yuqi Zhou et al.   JOURNAL OF INFECTIOUS DISEASES

NR4A transcription factors limit CAR T cell function in solid tumours

(2019) Joyce Chen et al.   NATURE

Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction

(2019) Xindong Liu et al.   NATURE

Eomes+T-betlow CD8+ T cells are functionally impaired and are associated with poor clinical outcome in patients with acute myeloid leukemia (AML)

(2019) Bei Jia et al.   CANCER RESEARCH

CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer

(2019) Laura M. McLane et al.   Annual Review of Immunology

Transforming Growth Factor-β Signaling in Immunity and Cancer

(2019) Eduard Batlle et al.   IMMUNITY

CD19 CAR T cell product and disease attributes predict leukemia remission durability

(2019) Olivia C. Finney et al.   JOURNAL OF CLINICAL INVESTIGATION

Impact of epitope density on CD8+ T cell development and function

(2019) Gabriela L. Cosma et al.   MOLECULAR IMMUNOLOGY

Modulation of chimeric antigen receptor surface expression by a small molecule switch

(2019) Alexandre Juillerat et al.   BMC BIOTECHNOLOGY

TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection

(2019) Francesca Alfei et al.   NATURE

TOX is a critical regulator of tumour-specific T cell differentiation

(2019) Andrew C. Scott et al.   NATURE

TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion

(2019) Omar Khan et al.   NATURE

Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection

(2019) Chen Yao et al.   NATURE IMMUNOLOGY

TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion

(2019) Hyungseok Seo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Regulation of CAR T cell-mediated cytokine release syndrome-like toxicity using low molecular weight adapters

(2019) Yong Gu Lee et al.   Nature Communications

CD4+ T cell exhaustion revealed by high PD-1 and LAG-3 expression and the loss of helper T cell function in chronic hepatitis B

(2019) Yuejiao Dong et al.   BMC IMMUNOLOGY

Clinical lessons learned from the first leg of the CAR T cell journey

(2019) Robbie G. Majzner et al.   NATURE MEDICINE

IFN-γ down-regulates the PD-1 expression and assist nivolumab in PD-1-blockade effect on CD8+ T-lymphocytes in pancreatic cancer

(2019) Guoping Ding et al.   BMC CANCER

TCF-1-Centered Transcriptional Network Drives an Effector versus Exhausted CD8 T Cell-Fate Decision

(2019) Zeyu Chen et al.   IMMUNITY

The Transcription Factor Tox2 Drives T Follicular Helper Cell Development via Regulating Chromatin Accessibility

(2019) Wei Xu et al.   IMMUNITY

Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity

(2019) Sitaram et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Determinants of response and resistance to CAR T cell therapy

(2019) Stefanie Lesch et al.   SEMINARS IN CANCER BIOLOGY

Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression

(2019) Nicolas Curdy et al.   TRENDS IN CELL BIOLOGY

CXCR3 enables recruitment and site-specific bystander activation of memory CD8+ T cells

(2019) Nicholas J. Maurice et al.   Nature Communications

Adoptive Transfer of Regulatory T Cells as a Promising Immunotherapy for the Treatment of Multiple Sclerosis

(2019) Samuel S. Duffy et al.   Frontiers in Neuroscience

Doxycycline Inducible Chimeric Antigen Receptor T Cells Targeting CD147 for Hepatocellular Carcinoma Therapy

(2019) Ren-Yu Zhang et al.   Frontiers in Cell and Developmental Biology

PD-1 disrupted CAR-T cells in the treatment of solid tumors: Promises and challenges

(2019) Eileen McGowan et al.   BIOMEDICINE & PHARMACOTHERAPY

Proliferating Transitory T Cells with an Effector-like Transcriptional Signature Emerge from PD-1+ Stem-like CD8+ T Cells during Chronic Infection

(2019) William H. Hudson et al.   IMMUNITY

CD4+ T Cell Help Is Required for the Formation of a Cytolytic CD8+ T Cell Subset that Protects against Chronic Infection and Cancer

(2019) Ryan Zander et al.   IMMUNITY

c-Jun overexpression in CAR T cells induces exhaustion resistance

(2019) Rachel C. Lynn et al.   NATURE

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

Dominant-Negative TGF-β Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication

(2018) Christopher C. Kloss et al.   MOLECULAR THERAPY

Rewiring T-cell responses to soluble factors with chimeric antigen receptors

(2018) ZeNan L Chang et al.   Nature Chemical Biology

Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia

(2018) Joseph A. Fraietta et al.   NATURE MEDICINE

Feasibility of controlling CD38-CAR T cell activity with a Tet-on inducible CAR design

(2018) Esther Drent et al.   PLoS One

Blockade of Tumor-Expressed PD-1 promotes lung cancer growth

(2018) Shisuo Du et al.   OncoImmunology

TGF-β in T Cell Biology: Implications for Cancer Immunotherapy

(2018) Amina Dahmani et al.   Cancers

Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo

(2018) Sarwish Rafiq et al.   NATURE BIOTECHNOLOGY

Tumor Antigen Escape from CAR T-cell Therapy

(2018) Robbie G. Majzner et al.   Cancer Discovery

Development of Inducible CD19-CAR T Cells with a Tet-On System for Controlled Activity and Enhanced Clinical Safety

(2018) Xingjian Gu et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory

(2018) Sophie Viaud et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Disruption of PD-1 Enhanced the Anti-tumor Activity of Chimeric Antigen Receptor T Cells Against Hepatocellular Carcinoma

(2018) Xingliang Guo et al.   Frontiers in Pharmacology

High Levels of Eomes Promote Exhaustion of Anti-tumor CD8+ T Cells

(2018) Jing Li et al.   Frontiers in Immunology

T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses

(2018) Alireza Saeidi et al.   Frontiers in Immunology

T Cell–Derived CD70 Delivers an Immune Checkpoint Function in Inflammatory T Cell Responses

(2017) Rachel E. O’Neill et al.   JOURNAL OF IMMUNOLOGY

Host-Derived CD70 Suppresses Murine Graft-versus-Host Disease by Limiting Donor T Cell Expansion and Effector Function

(2017) Nicholas D. Leigh et al.   JOURNAL OF IMMUNOLOGY

Inducible Caspase-9 Selectively Modulates the Toxicities of CD19-Specific Chimeric Antigen Receptor-Modified T Cells

(2017) Iulia Diaconu et al.   MOLECULAR THERAPY

Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection

(2017) Justin Eyquem et al.   NATURE

Chromatin states define tumour-specific T cell dysfunction and reprogramming

(2017) Mary Philip et al.   NATURE

Inducible Activation of MyD88 and CD40 in CAR T Cells Results in Controllable and Potent Antitumor Activity in Preclinical Solid Tumor Models

(2017) Melinda Mata et al.   Cancer Discovery

Cblb-deficient T cells are less susceptible to PD-L1-mediated inhibition

(2017) Sebastian Peer et al.   Oncotarget

CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells

(2017) Levi J. Rupp et al.   Scientific Reports

Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment

(2017) Oladapo O. Yeku et al.   Scientific Reports

Cbl-b Deficiency Mediates Resistance to Programed Death-Ligand 1/Programed Death-1 Regulation

(2017) Mai Fujiwara et al.   Frontiers in Immunology

Enhancement of PSMA-Directed CAR Adoptive Immunotherapy by PD-1/PD-L1 Blockade

(2017) Inna Serganova et al.   Molecular Therapy-Oncolytics

Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy

(2016) Oladapo O. Yeku et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition

(2016) Leonid Cherkassky et al.   JOURNAL OF CLINICAL INVESTIGATION

TGF 1-Mediated SMAD3 Enhances PD-1 Expression on Antigen-Specific T Cells in Cancer

(2016) B. V. Park et al.   Cancer Discovery

The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation

(2016) Kankana Bardhan et al.   Frontiers in Immunology

Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation

(2015) X. Zhou et al.   BLOOD

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor

(2015) C.-Y. Wu et al.   SCIENCE

Overcoming T cell exhaustion in infection and cancer

(2015) Kristen E. Pauken et al.   TRENDS IN IMMUNOLOGY

Modulation of Immune Cell Functions by the E3 Ligase Cbl-b

(2015) Christina Lutz-Nicoladoni et al.   Frontiers in Oncology

Cutting Edge: Dendritic Cells Prime a High Avidity CTL Response Independent of the Level of Presented Antigen

(2014) Charles J. Kroger et al.   JOURNAL OF IMMUNOLOGY

TGF-β upregulates CD70 expression and induces exhaustion of effector memory T cells in B-cell non-Hodgkin’s lymphoma

(2014) Z-Z Yang et al.   LEUKEMIA

Anti-PD-1 Antibody Therapy Potently Enhances the Eradication of Established Tumors By Gene-Modified T Cells

(2013) L. B. John et al.   CLINICAL CANCER RESEARCH

Clonal Exhaustion as a Mechanism to Protect Against Severe Immunopathology and Death from an Overwhelming CD8 T Cell Response

(2013) Markus Cornberg et al.   Frontiers in Immunology

Selective Effects of PD-1 on Akt and Ras Pathways Regulate Molecular Components of the Cell Cycle and Inhibit T Cell Proliferation

(2012) N. Patsoukis et al.   Science Signaling

Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma

(2011) C. U. Louis et al.   BLOOD

Increased sensitivity to antigen in high avidity CD8+ T cells results from augmented membrane proximal T-cell receptor signal transduction

(2011) Sharad K. Sharma et al.   IMMUNOLOGY

TOX Is Required for Development of the CD4 T Cell Lineage Gene Program

(2011) P. Aliahmad et al.   JOURNAL OF IMMUNOLOGY

T cell exhaustion

(2011) E John Wherry   NATURE IMMUNOLOGY

Memory CD8+ T cell differentiation

(2010) Joshua J. Obar et al.   Annals of the New York Academy of Sciences

One naive T cell, multiple fates in CD8+T cell differentiation

(2010) Carmen Gerlach et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Role of antigen persistence and dose for CD4+ T-cell exhaustion and recovery

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

PD-1 signaling in primary T cells

(2009) James L. Riley   IMMUNOLOGICAL REVIEWS

Chronic Antigen Stimulation Alone Is Sufficient to Drive CD8+ T Cell Exhaustion

(2009) C. M. Bucks et al.   JOURNAL OF IMMUNOLOGY