The pharmacology of second-generation chimeric antigen receptors

The Journey from Discoveries in Fundamental Immunology to Cancer Immunotherapy

(2015) Jacques F.A.P. Miller et al.   CANCER CELL

Inclusion of an IgG1-Fc spacer abrogates efficacy of CD19 CAR T cells in a xenograft mouse model

(2015) H Almåsbak et al.   GENE THERAPY

BRAF and MEK Inhibition Variably Affect GD2-specific Chimeric Antigen Receptor (CAR) T-Cell Function In Vitro

(2015) Tessa Gargett et al.   JOURNAL OF IMMUNOTHERAPY

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

4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors

(2015) Adrienne H Long et al.   NATURE MEDICINE

Individual Motile CD4 + T Cells Can Participate in Efficient Multikilling through Conjugation to Multiple Tumor Cells

(2015) Ivan Liadi et al.   Cancer Immunology Research

Identification of Chimeric Antigen Receptors That Mediate Constitutive or Inducible Proliferation of T Cells

(2015) M. J. Frigault et al.   Cancer Immunology Research

ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells

(2014) S. Guedan et al.   BLOOD

Current concepts in the diagnosis and management of cytokine release syndrome

(2014) D. W. Lee et al.   BLOOD

Adoptive Therapy With Chimeric Antigen Receptor–Modified T Cells of Defined Subset Composition

(2014) Stanley R. Riddell et al.   CANCER JOURNAL

NKG2D CARs as Cell Therapy for Cancer

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

Ipilimumab Plus Sargramostim vs Ipilimumab Alone for Treatment of Metastatic Melanoma

(2014) F. Stephen Hodi et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors

(2014) Alena Gros et al.   JOURNAL OF CLINICAL INVESTIGATION

Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab

(2014) Suzanne L. Topalian et al.   JOURNAL OF CLINICAL ONCOLOGY

A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors

(2014) Sven de Vos et al.   Journal of Hematology & Oncology

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

Regulation of Thymic NKT Cell Development by the B7-CD28 Costimulatory Pathway

(2014) J. A. Williams et al.   JOURNAL OF IMMUNOLOGY

Retargeting of Human T Cells to Tumor-Associated MUC1: The Evolution of a Chimeric Antigen Receptor

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

OX40 Drives Protective Vaccinia Virus-Specific CD8 T Cells

(2014) S. Salek-Ardakani et al.   JOURNAL OF IMMUNOLOGY

Antigen Sensitivity of CD22-Specific Chimeric TCR Is Modulated by Target Epitope Distance from the Cell Membrane

(2014) S. E. James et al.   JOURNAL OF IMMUNOLOGY

Control of Memory CD8+ T Cell Differentiation by CD80/CD86-CD28 Costimulation and Restoration by IL-2 during the Recall Response

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

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

(2014) S. R. Jacobs et al.   JOURNAL OF IMMUNOLOGY

ICOS Controls the Pool Size of Effector-Memory and Regulatory T Cells

(2014) Y. Burmeister et al.   JOURNAL OF IMMUNOLOGY

Differential Role of Th1 and Th2 Cytokines in Autotoxicity Driven by CD19-Specific Second-Generation Chimeric Antigen Receptor T Cells in a Mouse Model

(2014) E. J. Cheadle et al.   JOURNAL OF IMMUNOLOGY

IL-2: The First Effective Immunotherapy for Human Cancer

(2014) S. A. Rosenberg   JOURNAL OF IMMUNOLOGY

Bcl-6 directly represses the gene program of the glycolysis pathway

(2014) Kenneth J Oestreich et al.   NATURE IMMUNOLOGY

Mitigating the toxic effects of anticancer immunotherapy

(2014) Tara C. Gangadhar et al.   Nature Reviews Clinical Oncology

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

T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression

(2014) S. P. Santoro et al.   Cancer Immunology Research

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

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

Cytotoxic T Lymphocytes Block Tumor Growth Both by Lytic Activity and IFN -Dependent Cell-Cycle Arrest

(2014) H. Matsushita et al.   Cancer Immunology Research

Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study

(2013) C. R. Y. Cruz et al.   BLOOD

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation

(2013) J. N. Kochenderfer et al.   BLOOD

OX40 Is a Potent Immune-Stimulating Target in Late-Stage Cancer Patients

(2013) B. D. Curti et al.   CANCER RESEARCH

A Chimeric Receptor with NKG2D Specificity Enhances Natural Killer Cell Activation and Killing of Tumor Cells

(2013) Y.-H. Chang et al.   CANCER RESEARCH

Receptor Affinity and Extracellular Domain Modifications Affect Tumor Recognition by ROR1-Specific Chimeric Antigen Receptor T Cells

(2013) M. Hudecek et al.   CLINICAL CANCER RESEARCH

Agonist Antibodies to TNFR Molecules That Costimulate T and NK Cells

(2013) I. Melero 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

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

Chimeric NKG2D CAR-Expressing T Cell-Mediated Attack of Human Ovarian Cancer Is Enhanced by Histone Deacetylase Inhibition

(2013) De-Gang Song et al.   HUMAN GENE THERAPY

T Cell Exit from Quiescence and Differentiation into Th2 Cells Depend on Raptor-mTORC1-Mediated Metabolic Reprogramming

(2013) Kai Yang et al.   IMMUNITY

Uncoupling T-cell expansion from effector differentiation in cell-based immunotherapy

(2013) Joseph G. Crompton et al.   IMMUNOLOGICAL REVIEWS

Chimeric antigen receptor containing ICOS signaling domain mediates specific and efficient antitumor effect of T cells against EGFRvIII expressing glioma

(2013) Chan-Juan Shen et al.   Journal of Hematology & Oncology

Mouse Tumor Vasculature Expresses NKG2D Ligands and Can Be Targeted by Chimeric NKG2D-Modified T Cells

(2013) T. Zhang et al.   JOURNAL OF IMMUNOLOGY

T-helper-1-cell cytokines drive cancer into senescence

(2013) Heidi Braumüller et al.   NATURE

Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch

(2013) Patrick M Gubser et al.   NATURE IMMUNOLOGY

Advances in targeting cell surface signalling molecules for immune modulation

(2013) Sheng Yao et al.   NATURE REVIEWS DRUG DISCOVERY

Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia

(2013) Stephan A. Grupp et al.   NEW ENGLAND JOURNAL OF MEDICINE

CD19 CAR-Targeted T Cells Induce Long-Term Remission and B Cell Aplasia in an Immunocompetent Mouse Model of B Cell Acute Lymphoblastic Leukemia

(2013) Marco L. Davila et al.   PLoS One

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

Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo

(2013) E. Lanitis et al.   Cancer Immunology Research

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

(2012) H. J. Pegram et al.   BLOOD

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

Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

(2012) Ruben L Smeets et al.   BMC IMMUNOLOGY

Opposing Roles for TRAF1 in the AlternativeversusClassical NF-κB Pathway in T Cells

(2012) Ann J. McPherson et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

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

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

(2012) Christopher C Kloss et al.   NATURE BIOTECHNOLOGY

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

Redirecting T Cells to Ewing's Sarcoma Family of Tumors by a Chimeric NKG2D Receptor Expressed by Lentiviral Transduction or mRNA Transfection

(2012) Manfred Lehner et al.   PLoS One

Chimeric Antigen Receptor Therapy for B-cell Malignancies

(2012) David L Porter et al.   Journal of Cancer

How do CARs work?

(2012) Marco L. Davila et al.   OncoImmunology

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

CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo

(2011) D.-G. Song et al.   BLOOD

Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias

(2011) R. J. Brentjens et al.   BLOOD

In Vivo Persistence, Tumor Localization, and Antitumor Activity of CAR-Engineered T Cells Is Enhanced by Costimulatory Signaling through CD137 (4-1BB)

(2011) D.-G. Song et al.   CANCER RESEARCH

Roles of tumor necrosis factor receptor associated factor 3 (TRAF3) and TRAF5 in immune cell functions

(2011) Joanne M. Hildebrand et al.   IMMUNOLOGICAL REVIEWS

Costimulation by chimeric antigen receptors revisited the T cell antitumor response benefits from combined CD28-OX40 signalling

(2011) Andreas A. Hombach et al.   INTERNATIONAL JOURNAL OF CANCER

CD28 costimulation improves expansion and persistence of chimeric antigen receptor–modified T cells in lymphoma patients

(2011) Barbara Savoldo et al.   JOURNAL OF CLINICAL INVESTIGATION

Loss of the signaling adaptor TRAF1 causes CD8+T cell dysregulation during human and murine chronic infection

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

CD28 Costimulation Impairs the Efficacy of a Redirected T-cell Antitumor Attack in the Presence of Regulatory T cells Which Can Be Overcome by Preventing Lck Activation

(2011) David M Kofler et al.   MOLECULAR THERAPY

CARs on Track in the Clinic

(2011) Donald B Kohn et al.   MOLECULAR THERAPY

Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia

(2011) David L. Porter et al.   NEW ENGLAND JOURNAL OF MEDICINE

Trans-Endocytosis of CD80 and CD86: A Molecular Basis for the Cell-Extrinsic Function of CTLA-4

(2011) O. S. Qureshi et al.   SCIENCE

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

Antitransgene Rejection Responses Contribute to Attenuated Persistence of Adoptively Transferred CD20/CD19-Specific Chimeric Antigen Receptor Redirected T Cells in Humans

(2010) Michael C. Jensen et al.   BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

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

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

A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma

(2010) M. Hussein et al.   HAEMATOLOGICA

Dendritic Cells and Stat3 Are Essential for CD137-Induced CD8 T Cell Activation-Induced Cell Death

(2010) B. Zhang et al.   JOURNAL OF IMMUNOLOGY

The Optimal Antigen Response of Chimeric Antigen Receptors Harboring the CD3  Transmembrane Domain Is Dependent upon Incorporation of the Receptor into the Endogenous TCR/CD3 Complex

(2010) J. S. Bridgeman et al.   JOURNAL OF IMMUNOLOGY

Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety

(2010) V Hoyos et al.   LEUKEMIA

A phase I study of dacetuzumab (SGN-40, a humanized anti-CD40 monoclonal antibody) in patients with chronic lymphocytic leukemia

(2010) Richard R. Furman et al.   LEUKEMIA & LYMPHOMA

Crystal Structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 Complexes: Affinity, Specificity, and Regulation

(2010) Chao Zheng et al.   MOLECULAR CELL

T Cells Expressing Constitutively Active Akt Resist Multiple Tumor-associated Inhibitory Mechanisms

(2010) Jiali Sun et al.   MOLECULAR THERAPY

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

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

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

The Inducible Costimulator (ICOS) Is Critical for the Development of Human TH17 Cells

(2010) C. M. Paulos et al.   Science Translational Medicine

An Enigmatic Tail of CD28 Signaling

(2010) J. S. Boomer et al.   Cold Spring Harbor Perspectives in Biology

4-1BBL costimulation retrieves CD28 expression in activated T cells

(2009) Mojtaba Habib-Agahi et al.   CELLULAR IMMUNOLOGY

The promise and potential pitfalls of chimeric antigen receptors

(2009) Michel Sadelain et al.   CURRENT OPINION IN IMMUNOLOGY

4-1BB and CD28 Signaling Plays a Synergistic Role in Redirecting Umbilical Cord Blood T Cells Against B-Cell Malignancies

(2009) Syam Tammana et al.   HUMAN GENE THERAPY

Sequence, structure, function, immunity: structural genomics of costimulation

(2009) Kausik Chattopadhyay et al.   IMMUNOLOGICAL REVIEWS

Timing and tuning of CD27-CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology

(2009) Martijn A. Nolte et al.   IMMUNOLOGICAL REVIEWS

PD-1 signaling in primary T cells

(2009) James L. Riley   IMMUNOLOGICAL REVIEWS

Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells

(2009) Hélène Bour-Jordan et al.   IMMUNOLOGICAL REVIEWS

The Structure of the Trimer of Human 4-1BB Ligand Is Unique among Members of the Tumor Necrosis Factor Superfamily

(2009) Eun-Young Won et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phase I Study of the Humanized Anti-CD40 Monoclonal Antibody Dacetuzumab in Refractory or Recurrent Non-Hodgkin's Lymphoma

(2009) Ranjana Advani et al.   JOURNAL OF CLINICAL ONCOLOGY

CD137 Promotes Proliferation and Survival of Human B Cells

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

Chimeric NKG2D T Cells Require Both T Cell- and Host-Derived Cytokine Secretion and Perforin Expression to Increase Tumor Antigen Presentation and Systemic Immunity

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

A Herceptin-Based Chimeric Antigen Receptor with Modified Signaling Domains Leads to Enhanced Survival of Transduced T Lymphocytes and Antitumor Activity

(2009) Y. Zhao et al.   JOURNAL OF IMMUNOLOGY

Manufacturing Validation of Biologically Functional T Cells Targeted to CD19 Antigen for Autologous Adoptive Cell Therapy

(2009) Daniel Hollyman et al.   JOURNAL OF IMMUNOTHERAPY

Adoptive Immunotherapy of Disseminated Leukemia With TCR-transduced, CD8+ T Cells Expressing a Known Endogenous TCR

(2009) Michelle L Dossett et al.   MOLECULAR THERAPY

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

Chimeric Antigen Receptors Combining 4-1BB and CD28 Signaling Domains Augment PI3kinase/AKT/Bcl-XL Activation and CD8+ T Cell–mediated Tumor Eradication

(2009) Xiao-Song Zhong et al.   MOLECULAR THERAPY

Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains

(2009) C. Carpenito et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Stable transduction of quiescent T cells without induction of cycle progression by a novel lentiviral vector pseudotyped with measles virus glycoproteins

(2008) C. Frecha et al.   BLOOD

IFN-γ– and TNF-dependent bystander eradication of antigen-loss variants in established mouse cancers

(2008) Bin Zhang et al.   JOURNAL OF CLINICAL INVESTIGATION

Regulation of CD28 expression on CD8+ T cells by CTLA-4

(2007) M. Berg et al.   JOURNAL OF LEUKOCYTE BIOLOGY