Insight into next-generation CAR therapeutics: designing CAR T cells to improve clinical outcomes

Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B Cell Lymphoma

(2020) Max Topp et al.   BLOOD

Feasibility and efficacy of CD19-targeted CAR-T cells with concurrent ibrutinib for CLL after ibrutinib failure

(2020) Jordan Gauthier et al.   BLOOD

Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia

(2020) Xin He et al.   BLOOD

Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma

(2020) Jennifer N. Brudno et al.   NATURE MEDICINE

Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors

(2020) Enli Liu et al.   NEW ENGLAND JOURNAL OF MEDICINE

Human chimeric antigen receptor macrophages for cancer immunotherapy

(2020) Michael Klichinsky et al.   NATURE BIOTECHNOLOGY

Tuning the Antigen Density Requirement for CAR T-cell Activity

(2020) Robbie G. Majzner et al.   Cancer Discovery

Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel

(2020) Rawan Faramand et al.   CLINICAL CANCER RESEARCH

Eradication of neuroblastoma by T cells redirected with an optimized GD2-specific chimeric antigen receptor and interleukin-15

(2019) Yuhui Chen et al.   CLINICAL CANCER RESEARCH

An immunoproteomic approach to characterize the CAR interactome and signalosome

(2019) Maria C. Ramello et al.   Science Signaling

CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape

(2019) Mohamad Hamieh et al.   NATURE

Modulation of Target Antigen Density Improves CAR T Cell Functionality and Persistence

(2019) Sneha Ramakrishna et al.   CLINICAL CANCER RESEARCH

Armored Inducible Expression of IL-12 Enhances Antitumor Activity of Glypican-3–Targeted Chimeric Antigen Receptor–Engineered T Cells in Hepatocellular Carcinoma

(2019) Ying Liu et al.   JOURNAL OF IMMUNOLOGY

Chimeric Antigen Receptors Incorporating D Domains Targeting CD123 Direct Potent Mono- and Bi-specific Antitumor Activity of T Cells

(2019) Haiying Qin et al.   MOLECULAR THERAPY

A safe and potent anti-CD19 CAR T cell therapy

(2019) Zhitao Ying et al.   NATURE MEDICINE

Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice

(2019) Yushu Joy Xie et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

CAR T-Cells Targeting the Integrin αvβ6 and Co-Expressing the Chemokine Receptor CXCR2 Demonstrate Enhanced Homing and Efficacy against Several Solid Malignancies

(2019) Lynsey M. Whilding et al.   Cancers

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

(2019) Alexandre Juillerat et al.   BMC BIOTECHNOLOGY

CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity

(2019) Bryan D. Choi et al.   NATURE BIOTECHNOLOGY

The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells

(2019) Katrin Mestermann et al.   Science Translational Medicine

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

(2019) Yong Gu Lee et al.   Nature Communications

CAR-T Engineering: Optimizing Signal Transduction and Effector Mechanisms

(2019) Emiliano Roselli et al.   BIODRUGS

Sequential CD19-22 CAR T therapy induces sustained remission in children with r/r B-ALL

(2019) Jing Pan et al.   BLOOD

CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity

(2019) Wenyan Fu et al.   Nature Communications

Engineering strategies to overcome the current roadblocks in CAR T cell therapy

(2019) Sarwish Rafiq et al.   Nature Reviews Clinical Oncology

Nucleofection with Plasmid DNA for CRISPR/Cas9-Mediated Inactivation of Programmed Cell Death Protein 1 in CD133-Specific CAR T Cells

(2018) Bian Hu et al.   HUMAN GENE THERAPY

Myeloid-Derived Suppressor Cells: Immune-Suppressive Cells That Impair Antitumor Immunity and Are Sculpted by Their Environment

(2018) Suzanne Ostrand-Rosenberg et al.   JOURNAL OF IMMUNOLOGY

IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor

(2018) Keishi Adachi et al.   NATURE BIOTECHNOLOGY

Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells

(2018) Margherita Norelli et al.   NATURE MEDICINE

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

CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade

(2018) Theodoros Giavridis et al.   NATURE MEDICINE

Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer

(2018) Rohtesh S. Mehta et al.   Frontiers in Immunology

The Pharmacology of T Cell Therapies

(2018) Michael C. Milone et al.   Molecular Therapy-Methods & Clinical Development

CD19 CAR T Cells Expressing IL-12 Eradicate Lymphoma in Fully Lymphoreplete Mice through Induction of Host Immunity

(2018) Gray Kueberuwa et al.   Molecular Therapy-Oncolytics

In vivo fate and activity of second versus third-generation D19-specific CAR-T cells in B-cell non-Hodgkin lymphomas

(2018) Carlos A. Ramos et al.   MOLECULAR THERAPY

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

Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function

(2018) Alexander I. Salter et al.   Science Signaling

Tumor Antigen Escape from CAR T-cell Therapy

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

ASBMT Consensus Grading for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells

(2018) Daniel W Lee et al.   BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts

(2018) Rosalie M. Sterner et al.   BLOOD

CRISPR/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions

(2018) Wanghong Hu et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization

(2018) Miguel F. Sanmamed et al.   CELL

Preventing Lck Activation in CAR T Cells Confers Treg Resistance but Requires 4-1BB Signaling for Them to Persist and Treat Solid Tumors in Nonlymphodepleted Hosts

(2018) Carter M. Suryadevara et al.   CLINICAL CANCER RESEARCH

Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial

(2018) Frederick L Locke et al.   LANCET ONCOLOGY

Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency

(2018) Judith Feucht et al.   NATURE MEDICINE

Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

(2018) Stephen J. Schuster et al.   NEW ENGLAND JOURNAL OF MEDICINE

Preclinical Development of Bivalent Chimeric Antigen Receptors Targeting Both CD19 and CD22

(2018) Haiying Qin et al.   Molecular Therapy-Oncolytics

FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease

(2018) Emily Y. Jen et al.   CLINICAL CANCER RESEARCH

Designed Ankyrin Repeat Proteins as Her2 Targeting Domains in Chimeric Antigen Receptor-Engineered T Cells

(2017) Elizabeth Siegler et al.   HUMAN GENE 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

Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains

(2017) Leah Alabanza et al.   MOLECULAR THERAPY

Chimeric antigen receptor T-cell therapy — assessment and management of toxicities

(2017) Sattva S. Neelapu et al.   Nature Reviews Clinical Oncology

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

(2017) Sattva S. Neelapu et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

CAR T Cells Releasing IL-18 Convert to T-Bet high FoxO1 low Effectors that Exhibit Augmented Activity against Advanced Solid Tumors

(2017) Markus Chmielewski et al.   Cell Reports

Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18

(2017) Biliang Hu et al.   Cell Reports

High-Affinity GD2-Specific CAR T Cells Induce Fatal Encephalitis in a Preclinical Neuroblastoma Model

(2017) Sarah A. Richman et al.   Cancer Immunology Research

Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer

(2017) Julia Tchou et al.   Cancer Immunology Research

Transgenic Expression of IL15 Improves Antiglioma Activity of IL13Rα2-CAR T Cells but Results in Antigen Loss Variants

(2017) Giedre Krenciute et al.   Cancer Immunology Research

Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity

(2017) Spencer Park et al.   Scientific Reports

Repeated loss of target surface antigen after immunotherapy in primary mediastinal large B cell lymphoma

(2016) Hui Yu et al.   AMERICAN JOURNAL OF HEMATOLOGY

Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia

(2016) Joseph A. Fraietta et al.   BLOOD

Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery

(2016) S C Katz et al.   CANCER GENE THERAPY

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

(2016) Kole T. Roybal et al.   CELL

Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors

(2016) Kole T. Roybal et al.   CELL

CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells

(2016) Xiaojuan Liu et al.   CELL RESEARCH

Regulatory T cells in cancer immunotherapy

(2016) Atsushi Tanaka et al.   CELL RESEARCH

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

(2016) Jiangtao Ren et al.   CLINICAL CANCER RESEARCH

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

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

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

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

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

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

T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells

(2016) E. Zah et al.   Cancer Immunology Research

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

Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric Antigen Receptor-Modified T-cell Therapy for CEA+ Liver Metastases

(2015) S. C. Katz et al.   CLINICAL CANCER RESEARCH

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

(2015) Ignazio Caruana et al.   NATURE MEDICINE

The pharmacology of second-generation chimeric antigen receptors

(2015) Sjoukje J. C. van der Stegen et al.   NATURE REVIEWS DRUG DISCOVERY

Adoptive cell transfer as personalized immunotherapy for human cancer

(2015) S. A. Rosenberg et al.   SCIENCE

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

(2015) E. Sotillo et al.   Cancer Discovery

IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumorsin vivo

(2015) Mythili Koneru et al.   OncoImmunology

Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors

(2015) Joanne A. Hammill et al.   Journal for ImmunoTherapy of Cancer

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

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

Design of a Phase I Clinical Trial to Evaluate Intratumoral Delivery of ErbB-Targeted Chimeric Antigen Receptor T-Cells in Locally Advanced or Recurrent Head and Neck Cancer

(2013) May C.I. van Schalkwyk et al.   Human Gene Therapy Clinical Development

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

(2012) H. J. Pegram et al.   BLOOD

A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR

(2012) H. Torikai et al.   BLOOD

Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents

(2012) Zahra Sharifzadeh et al.   CANCER LETTERS

Local Delivery of lnterleukin-12 Using T Cells Targeting VEGF Receptor-2 Eradicates Multiple Vascularized Tumors in Mice

(2012) D. Chinnasamy et al.   CLINICAL CANCER RESEARCH

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

(2012) Christopher C Kloss et al.   NATURE BIOTECHNOLOGY

OX40 costimulation by a chimeric antigen receptor abrogates CD28 and IL-2 induced IL-10 secretion by redirected CD4+T cells

(2012) Andreas A. Hombach et al.   OncoImmunology

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

(2011) D.-G. Song et al.   BLOOD

Expression of a Functional CCR2 Receptor Enhances Tumor Localization and Tumor Eradication by Retargeted Human T cells Expressing a Mesothelin-Specific Chimeric Antibody Receptor

(2011) E. K. Moon et al.   CLINICAL CANCER RESEARCH

Inducible Apoptosis as a Safety Switch for Adoptive Cell Therapy

(2011) Antonio Di Stasi et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

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