CAR-T cell therapy research

Extracellular Domains of CAR Reprogram T-Cell Metabolism Without Antigen Stimulation

This study shows that CAR extracellular domains reprogram T-cell metabolism independently of antigen stimulation, with distinct metabolic effects observed between different CARs.

A Multiscale Protein Abundance Structured Population Kinetic Model Systematically Explores the Design Space of Constitutive and Inducible CAR-T cells

This paper develops a framework called PASCAR to systematically explore CAR-T cell design space using multiscale models and optimization, showing intermediate CAR affinities reduce healthy cell lysis while maintaining tumor cell killing.

Drug-Mediated Control of Receptor Valency Enhances Immune Cell Potency

This paper develops valency-controlled receptors (VCRs) to enhance CAR functionality by modulating T cell signaling through multivalent ligands, showing improved immune response against tumors.

Exploring the rules of chimeric antigen receptor phenotypic output using combinatorial signaling motif libraries and machine learning

The paper uses synthetic costimulatory domains and machine learning to identify design rules for CARs that enhance cytotoxicity and stemness.

High-throughput mutagenesis identifies mutations and RNA binding proteins controlling CD19 splicing and CART-19 therapy resistance

The paper identifies mutations and RNA-binding proteins affecting CD19 splicing and CART-19 therapy resistance through high-throughput mutagenesis and mathematical modeling.

Engineering clinically-approved drug gated CAR circuits

The paper develops drug-gated CAR circuits using NS3 protease domains and FDA-approved inhibitors to enhance CAR T cell therapy safety and specificity.

Coopting T cell proximal signaling molecules enables Boolean logic-gated CAR T cell control

This paper introduces a novel CAR T cell platform using proximal T cell signaling molecules to enable Boolean logic-gated control, improving efficacy and reducing off-tumor toxicity.

Physiological (TCR-like) regulated lentiviral vectors for the generation of improved CAR-T cells

This paper develops lentiviral vectors with TCR-like expression patterns to generate CAR-T cells with reduced tonic signaling and improved therapeutic profiles.

De novo designed transmembrane domains tune engineered receptor functions

The paper designs transmembrane domains to control receptor function, showing that oligomeric state affects CAR T cell activity and cytokine release.

Sense-and-respond payload delivery using a novel antigen-inducible promoter improves suboptimal CAR-T activation

This paper introduces a novel antigen-inducible promoter to enhance CAR-T cell activation in low-immunogenic environments, showing improved cytokine expression and T cell proliferation.

Modeling predicts differences in CAR T cell signaling due to biological variability

The paper uses mathematical modeling to show that CD28-bearing CARs lead to faster and more consistent T cell responses under variability, with LCK activity influencing response times.

In vitro assessment of an engineered tBID-based safety switch system in human T lymphocytes

This study develops and tests a tBID-based safety switch system for engineered T cells to manage toxicity and persistence, showing up to 90% cell elimination in vitro.

Pan-cancer analysis of patient tumor single-cell transcriptomes identifies promising selective and safe CAR targets in head and neck cancer

The paper analyzes pan-cancer single-cell transcriptomes to evaluate and identify new CAR targets for head and neck cancer, finding five promising targets with superior selectivity and safety.

Clonal hematopoiesis is associated with increased toxicity in large B-cell lymphoma patients treated with chimeric antigen receptor T cell therapy

This study finds that clonal hematopoiesis mutations, particularly in DNMT3A, TET2, and ASXL1, are linked to increased toxicity in patients undergoing anti-CD19 CAR T-cell therapy for large B-cell lymphoma.

Vectofusin-1 based T-cell transduction approach for generating murine chimeric antigen receptor T-cells for cancer.

This study evaluates vectofusin-1 as a transduction enhancer for generating murine CAR-T cells, finding it comparable to Retronectin.

speedingCARs: accelerating the engineering of CAR T cells by signaling domain shuffling and single-cell sequencing

speedingCARs uses domain shuffling and single-cell sequencing to engineer CAR T cells, identifying effective variants with diverse transcriptional signatures and T cell phenotypes.

Brain capillary obstruction as a novel mechanism of anti-CD19 CAR T cell neurotoxicity

This study identifies brain capillary obstruction and hypoxia as mechanisms of neurotoxicity in CD19-CAR T cell therapy using a mouse model.

Base-edited CAR T Cells for combinational therapy against T cell malignancies

This study develops base-edited CAR T cells to overcome fratricide by removing shared antigens, showing enhanced cytotoxicity against T cell malignancies.

Hypoxia-Sensing CAR T-Cells Provide Safety and Efficacy in Treating Solid Tumors

This paper develops hypoxia-sensing CAR T-cells that selectively target solid tumors without off-tumor toxicity using murine xenograft models.

T cell circuits that sense antigen density with an ultrasensitive threshold

This paper engineers T cells with a two-step positive feedback circuit to kill target cells based on an ultrasensitive antigen density threshold.

ERK activation in CAR T cells is amplified by CD28-mediated increase in CD3ζ phosphorylation

The paper constructs a computational model of CAR T cell activation, showing CD28 enhances ERK activation by increasing CD3ζ phosphorylation kinetics.

Inducible gene switches with memory in human T cells for cellular immunotherapy

This paper introduces gene circuits with memory to control gene expression in T cells, demonstrating regulation of CAR expression and T cell activity using an FDA-approved drug.

Computational model of chimeric antigen receptors explains site-specific phosphorylation kinetics

The paper develops a computational model to explain site-specific phosphorylation kinetics of CARs using phospho-proteomic data and mechanistic modeling.

CAR T Cells Secreting IL18 Augment Antitumor Immunity and Increase T Cell Proliferation and Costimulation

This study shows that IL18-expressing CAR T cells enhance antitumor immunity, T cell proliferation, and costimulation, while reducing GVHD risk through a novel strategy.