Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy

Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy

(2017) Paul A. Beavis et al.   JOURNAL OF CLINICAL INVESTIGATION

Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas

(2017) Gary Kohanbash et al.   JOURNAL OF CLINICAL INVESTIGATION

Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor–Modified T Cells After Failure of Ibrutinib

(2017) Cameron J. Turtle et al.   JOURNAL OF CLINICAL ONCOLOGY

Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels

(2017) James N. Kochenderfer et al.   JOURNAL OF CLINICAL ONCOLOGY

A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization

(2017) Esther Drent et al.   MOLECULAR THERAPY

CAR T Cells Administered in Combination with Lymphodepletion and PD-1 Inhibition to Patients with Neuroblastoma

(2017) Andras Heczey et al.   MOLECULAR THERAPY

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

(2017) Iulia Diaconu et al.   MOLECULAR THERAPY

Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy

(2017) James N. Kochenderfer et al.   MOLECULAR THERAPY

Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma

(2017) Frederick L. Locke et al.   MOLECULAR THERAPY

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

(2017) Justin Eyquem et al.   NATURE

Therapeutic T cell engineering

(2017) Michel Sadelain et al.   NATURE

A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

(2017) Donald M. O’Rourke et al.   Science Translational Medicine

Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity

(2017) Dmitriy Zamarin et al.   Nature Communications

Endothelial Activation and Blood–Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells

(2017) Juliane Gust et al.   Cancer Discovery

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

An oxygen sensitive self-decision making engineered CAR T-cell

(2017) Alexandre Juillerat et al.   Scientific Reports

CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

(2017) Yongping Zhang et al.   Frontiers of Medicine

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells

(2017) Xinru Wei et al.   OncoImmunology

HER2-Specific Chimeric Antigen Receptor–Modified Virus-Specific T Cells for Progressive Glioblastoma

(2017) Nabil Ahmed et al.   JAMA Oncology

A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines

(2017) Dina Schneider et al.   Journal for ImmunoTherapy of Cancer

T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma

(2016) S. A. Ali et al.   BLOOD

Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy

(2016) R. Gardner et al.   BLOOD

Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade

(2016) Haidong Tang et al.   CANCER CELL

A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors

(2016) Xiaojun Liu et al.   CANCER RESEARCH

Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits

(2016) Kole T. Roybal et al.   CELL

Analysis of ROR1 Protein Expression in Human Cancer and Normal Tissues

(2016) Ashwini Balakrishnan et al.   CLINICAL CANCER RESEARCH

Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition

(2016) Jiangtao Ren et al.   CLINICAL CANCER RESEARCH

Interleukin-35 Limits Anti-Tumor Immunity

(2016) Meghan E. Turnis et al.   IMMUNITY

Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells

(2016) Omkar U. Kawalekar et al.   IMMUNITY

Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy

(2016) Christina Pfirschke et al.   IMMUNITY

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia

(2016) Paulina J. Paszkiewicz et al.   JOURNAL OF CLINICAL INVESTIGATION

CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients

(2016) Cameron J. Turtle et al.   JOURNAL OF CLINICAL INVESTIGATION

Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies

(2016) Marco Ruella et al.   JOURNAL OF CLINICAL INVESTIGATION

Ionic immune suppression within the tumour microenvironment limits T cell effector function

(2016) Robert Eil et al.   NATURE

Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy

(2016) Christine E. Brown et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mutational landscape ofEGFR-,MYC-, andKras-driven genetically engineered mouse models of lung adenocarcinoma

(2016) David G. McFadden et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8 + and CD4 + CD19-specific chimeric antigen receptor–modified T cells

(2016) Cameron J. Turtle et al.   Science Translational Medicine

Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model

(2016) Eloah Rabello Suarez et al.   Oncotarget

Augmentation of CAR T-cell Trafficking and Antitumor Efficacy by Blocking Protein Kinase A Localization

(2016) K. Newick et al.   Cancer Immunology Research

VEGF Neutralization Plus CTLA-4 Blockade Alters Soluble and Cellular Factors Associated with Enhancing Lymphocyte Infiltration and Humoral Recognition in Melanoma

(2016) X. Wu et al.   Cancer Immunology Research

A Tet-On Inducible System for Controlling CD19-Chimeric Antigen Receptor Expression upon Drug Administration

(2016) R. Sakemura et al.   Cancer Immunology Research

Reduction of MDSCs with All-trans Retinoic Acid Improves CAR Therapy Efficacy for Sarcomas

(2016) A. H. Long et al.   Cancer Immunology Research

Design of chimeric antigen receptors with integrated controllable transient functions

(2016) Alexandre Juillerat et al.   Scientific Reports

Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells

(2015) Zeguo Zhao et al.   CANCER CELL

Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T

(2015) Rachel A. Burga et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice

(2015) X. Liu et al.   CANCER RESEARCH

Human Epidermal Growth Factor Receptor 2 (HER2) –Specific Chimeric Antigen Receptor–Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma

(2015) Nabil Ahmed et al.   JOURNAL OF CLINICAL ONCOLOGY

Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor

(2015) James N. Kochenderfer et al.   JOURNAL OF CLINICAL ONCOLOGY

Coexpressed Catalase Protects Chimeric Antigen Receptor–Redirected T Cells as well as Bystander Cells from Oxidative Stress–Induced Loss of Antitumor Activity

(2015) Maarten A. Ligtenberg et al.   JOURNAL OF IMMUNOLOGY

A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16ecto directed chimeric antigen receptors for recurrent ovarian cancer

(2015) Mythili Koneru et al.   Journal of Translational Medicine

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial

(2015) Daniel W Lee et al.   LANCET

Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo

(2015) D Sommermeyer et al.   LEUKEMIA

Enhancing Antitumor Efficacy of Chimeric Antigen Receptor T Cells Through Constitutive CD40L Expression

(2015) Kevin J Curran et al.   MOLECULAR THERAPY

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

(2015) Stefani Spranger et al.   NATURE

Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes

(2015) Ignazio Caruana et al.   NATURE MEDICINE

Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients

(2015) Emanuela Romano et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

(2015) C.-Y. Wu et al.   SCIENCE

Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia

(2015) David L. Porter et al.   Science Translational Medicine

Engineering CAR-T cells: Design concepts

(2015) Shivani Srivastava et al.   TRENDS IN IMMUNOLOGY

Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy

(2015) E. Sotillo et al.   Cancer Discovery

Radio-Immunotherapy-Induced Immunogenic Cancer Cells as Basis for Induction of Systemic Anti-Tumor Immune Responses – Pre-Clinical Evidence and Ongoing Clinical Applications

(2015) Anja Derer et al.   Frontiers in Immunology

Comparison of naïve and central memory derived CD8+effector cell engraftment fitness and function following adoptive transfer

(2015) Xiuli Wang et al.   OncoImmunology

Tumor-Targeted Human T Cells Expressing CD28-Based Chimeric Antigen Receptors Circumvent CTLA-4 Inhibition

(2015) Maud Condomines et al.   PLoS One

Current concepts in the diagnosis and management of cytokine release syndrome

(2014) D. W. Lee et al.   BLOOD

NKG2D CARs as Cell Therapy for Cancer

(2014) Charles L. Sentman et al.   CANCER JOURNAL

Armed Oncolytic Virus Enhances Immune Functions of Chimeric Antigen Receptor-Modified T Cells in Solid Tumors

(2014) N. Nishio et al.   CANCER RESEARCH

Genetic Modification of T Cells Redirected toward CS1 Enhances Eradication of Myeloma Cells

(2014) J. Chu et al.   CLINICAL CANCER RESEARCH

Multifactorial T-cell Hypofunction That Is Reversible Can Limit the Efficacy of Chimeric Antigen Receptor-Transduced Human T cells in Solid Tumors

(2014) E. K. Moon et al.   CLINICAL CANCER RESEARCH

Serial Transfer of Single-Cell-Derived Immunocompetence Reveals Stemness of CD8+ Central Memory T Cells

(2014) Patricia Graef et al.   IMMUNITY

Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry

(2014) Charlotte Giesen et al.   NATURE METHODS

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia

(2014) Shannon L. Maude et al.   NEW ENGLAND JOURNAL OF MEDICINE

Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia

(2014) M. L. Davila et al.   Science Translational Medicine

Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity

(2014) P. S. Adusumilli et al.   Science Translational Medicine

The Nonsignaling Extracellular Spacer Domain of Chimeric Antigen Receptors Is Decisive for In Vivo Antitumor Activity

(2014) M. Hudecek et al.   Cancer Immunology Research

Safety of Targeting ROR1 in Primates with Chimeric Antigen Receptor-Modified T Cells

(2014) C. Berger et al.   Cancer Immunology Research

Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor

(2013) Sarah Tettamanti et al.   BRITISH JOURNAL OF HAEMATOLOGY

Enhanced Effector Responses in Activated CD8+ T Cells Deficient in Diacylglycerol Kinases

(2013) M. J. Riese et al.   CANCER RESEARCH

B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma

(2013) R. O. Carpenter et al.   CLINICAL CANCER RESEARCH

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

Genetically engineered mouse models of cancer reveal new insights about the antitumor immune response

(2013) Michel DuPage et al.   CURRENT OPINION IN IMMUNOLOGY

Adoptive Immunotherapy with Redirected T Cells Produces CCR7− Cells That Are Trapped in the Periphery and Benefit from Combined CD28-OX40 Costimulation

(2013) Andreas A. Hombach et al.   HUMAN GENE THERAPY

Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma

(2013) Tyler R. Simpson et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Combinational Targeting Offsets Antigen Escape and Enhances Effector Functions of Adoptively Transferred T Cells in Glioblastoma

(2013) Meenakshi Hegde et al.   MOLECULAR THERAPY

Persistence and Efficacy of Second Generation CAR T Cell Against the LeY Antigen in Acute Myeloid Leukemia

(2013) David S. Ritchie et al.   MOLECULAR THERAPY

Kinetics of Tumor Destruction by Chimeric Antigen Receptor-modified T Cells

(2013) Usanarat Anurathapan et al.   MOLECULAR THERAPY

Co-Introduced Functional CCR2 Potentiates In Vivo Anti-Lung Cancer Functionality Mediated by T Cells Double Gene-Modified to Express WT1-Specific T-Cell Receptor

(2013) Hiroaki Asai et al.   PLoS One

Disparate Individual Fates Compose Robust CD8+ T Cell Immunity

(2013) V. R. Buchholz et al.   SCIENCE

Heterogeneous Differentiation Patterns of Individual CD8+ T Cells

(2013) C. Gerlach et al.   SCIENCE

PD-1- and CTLA-4-Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses

(2013) V. D. Fedorov et al.   Science Translational Medicine

CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia

(2013) R. J. Brentjens et al.   Science Translational Medicine

Mesothelin-Specific Chimeric Antigen Receptor mRNA-Engineered T Cells Induce Antitumor Activity in Solid Malignancies

(2013) G. L. Beatty et al.   Cancer Immunology Research

Targeting Fibroblast Activation Protein in Tumor Stroma with Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth and Augment Host Immunity without Severe Toxicity

(2013) L.-C. S. Wang et al.   Cancer Immunology Research

TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer Immunotherapy

(2013) Zakaria Grada et al.   Molecular Therapy-Nucleic Acids

Blockade of PD-1 immunosuppression boosts CAR T-cell therapy

(2013) Liza B John et al.   OncoImmunology

Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning

(2012) H. J. Pegram et al.   BLOOD

Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance

(2012) Elizabeth S. Nakasone et al.   CANCER CELL

Distribution and Compartmentalization of Human Circulating and Tissue-Resident Memory T Cell Subsets

(2012) Taheri Sathaliyawala et al.   IMMUNITY

Dual Targeting of ErbB2 and MUC1 in Breast Cancer Using Chimeric Antigen Receptors Engineered to Provide Complementary Signaling

(2012) Scott Wilkie et al.   JOURNAL OF CLINICAL IMMUNOLOGY

An NKp30-Based Chimeric Antigen Receptor Promotes T Cell Effector Functions and Antitumor Efficacy In Vivo

(2012) T. Zhang et al.   JOURNAL OF IMMUNOLOGY

Tumor PD-L1 co-stimulates primary human CD8+ cytotoxic T cells modified to express a PD1:CD28 chimeric receptor

(2012) Megan E. Prosser et al.   MOLECULAR IMMUNOLOGY

Unknown

(2012) David Davies et al.   MOLECULAR MEDICINE

Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells

(2012) Christopher C Kloss et al.   NATURE BIOTECHNOLOGY

B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells

(2011) J. N. Kochenderfer et al.   BLOOD

Endogenous T Cell Responses to Antigens Expressed in Lung Adenocarcinomas Delay Malignant Tumor Progression

(2011) Michel DuPage et al.   CANCER CELL

IL-12 Release by Engineered T Cells Expressing Chimeric Antigen Receptors Can Effectively Muster an Antigen-Independent Macrophage Response on Tumor Cells That Have Shut Down Tumor Antigen Expression

(2011) M. Chmielewski et al.   CANCER RESEARCH

The ICOS/ICOSL Pathway Is Required for Optimal Antitumor Responses Mediated by Anti-CTLA-4 Therapy

(2011) T. Fu et al.   CANCER RESEARCH

Single-Chain Antibody-Based Immunotoxins Targeting Her2/neu: Design Optimization and Impact of Affinity on Antitumor Efficacy and Off-Target Toxicity

(2011) Y. Cao et al.   MOLECULAR CANCER THERAPEUTICS

A human memory T cell subset with stem cell–like properties

(2011) Luca Gattinoni et al.   NATURE MEDICINE

T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia

(2011) M. Kalos et al.   Science Translational Medicine

Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia

(2010) Q. Zhou et al.   BLOOD

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19

(2010) J. N. Kochenderfer et al.   BLOOD

Tumor-Specific CD8+ T Cells Expressing Interleukin-12 Eradicate Established Cancers in Lymphodepleted Hosts

(2010) S. P. Kerkar et al.   CANCER RESEARCH

Spatiotemporal Basis of CTLA-4 Costimulatory Molecule-Mediated Negative Regulation of T Cell Activation

(2010) Tadashi Yokosuka et al.   IMMUNITY

Enhanced Tumor Trafficking of GD2 Chimeric Antigen Receptor T Cells by Expression of the Chemokine Receptor CCR2b

(2010) John A. Craddock et al.   JOURNAL OF IMMUNOTHERAPY

Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2

(2010) Richard A Morgan et al.   MOLECULAR THERAPY

T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model

(2009) A. Di Stasi et al.   BLOOD

Chimeric Receptors Containing CD137 Signal Transduction Domains Mediate Enhanced Survival of T Cells and Increased Antileukemic Efficacy In Vivo

(2009) Michael C. Milone et al.   MOLECULAR THERAPY

Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase

(2009) Michel DuPage et al.   Nature Protocols

Anti-CTLA-4 therapy results in higher CD4+ICOShiT cell frequency and IFN-γ levels in both nonmalignant and malignant prostate tissues

(2009) Hong Chen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates

(2008) Carolina Berger et al.   JOURNAL OF CLINICAL INVESTIGATION

Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma

(2008) Martin A Pule et al.   NATURE MEDICINE

CTLA-4 blockade increases IFN -producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients

(2008) C. I. Liakou et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA