our Premium Content: News alerts, weekly reports and conference planners

GENE:

CARS1 (Cysteinyl-TRNA Synthetase 1)

News alerts, weekly reports and conference planners

1year

Results From First-in-Human Phase I Study of a Novel CD19-1XX Chimeric Antigen Receptor With Calibrated Signaling in Large B-Cell Lymphoma. (PubMed, J Clin Oncol)

The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses with favorable toxicity profiles and may benefit the treatment of other hematologic malignancies, solid tumors, and autoimmunity.

1 year ago

P1 data • Journal

CD8 (cluster of differentiation 8) • CARS1 (Cysteinyl-TRNA Synthetase 1)

2years

Modifying CAR-T cells with anti-checkpoints in cancer immunotherapy: A focus on anti PD-1/PD-L1 antibodies. (PubMed, Life Sci)

Those CARs expressing single chain variable fragments (scFvs) or nanobodies against immune checkpoint stimulatory or inhibitory molecules, such as the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling axis are being extensively studied in various clinical trials. In this review, we discuss the significance of anti-PD-(L)1 scFv-expressing CAR-T cells in the treatment of human cancers, describing current challenges and potential strategies to overcome such predicaments in the area of cancer immunotherapy.

2 years ago

Review • Journal • CAR T-Cell Therapy

PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • CARS1 (Cysteinyl-TRNA Synthetase 1)

over2years

Development of a Regulated, Optimized Mesothelin Chimeric Antigen Receptor (CAR) for the Treatment of Mesothelin Positive Cancers (ASH 2023)

Contrary to the conclusions of prior studies with MSLN-targeted CARs, membrane distal epitopes were superior to membrane proximal epitopes when binders were paired with the correct spacer, and shed MSLN and MUC16 were not inhibitory for the best-performing CARs, regardless of target epitope. Furthermore, regulated expression enhanced the potency and durability of response compared to constitutive expression. This approach may improve CAR activity in patients with MSLN+ solid tumors or leukemia.

over 2 years ago

PD(L)-1 Biomarker • IO biomarker

IFNG (Interferon, gamma) • MSLN (Mesothelin) • MUC16 (Mucin 16, Cell Surface Associated) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • IL2 (Interleukin 2) • ICAM1 (Intercellular adhesion molecule 1) • CARS1 (Cysteinyl-TRNA Synthetase 1) • CD58 (CD58 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)

MSLN positive • PD-1 elevation

over2years

Expression of a Novel Chimeric Inhibitory Receptor Attenuates CD19 CAR T Cells: A Promising Strategy for Toxicity Mitigation (ASH 2023)

Tocilizumab is the only FDA-approved drug for CRS and despite concurrent corticosteroids, often fails to control CRS...We observed that monocyte-derived macrophage and DC activation by CD19 CAR/CIR T cells was reduced as evidenced by decreased secretion of proinflammatory cytokines and chemokines. Conclusion These results provide a compelling proof of concept of a novel self-regulating CAR T cell design with the potential to mitigate severe toxicities in patients.

over 2 years ago

CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • CD19 (CD19 Molecule) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • TNFA (Tumor Necrosis Factor-Alpha) • IL2RA (Interleukin 2 receptor, alpha) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD69 (CD69 Molecule) • IL7R (Interleukin 7 Receptor) • CCR7 (Chemokine (C-C motif) receptor 7) • CD14 (CD14 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1) • CSF2 (Colony stimulating factor 2) • CARS1 (Cysteinyl-TRNA Synthetase 1) • FAS (Fas cell surface death receptor) • IL17A (Interleukin 17A)

Actemra IV (tocilizumab)

over2years

HGF-Based CAR-T Cells Target Hepatocellular Carcinoma Cells That Express High Levels of c-Met. (PubMed, Immunol Invest)

Correspondingly, overexpression of c-Met in the embryonic kidney cell line HEK293T led to their enhanced killing by NK1 CAR-T cells. Our studies demonstrate that a minimal amino-terminal polypeptide sequence comprising the kirngle1 domain of HGF is highly relevant to the design of effective CAR-T cell therapies that kill HCC cells expressing high levels of c-Met.

over 2 years ago

Journal • CAR T-Cell Therapy • IO biomarker

MET (MET proto-oncogene, receptor tyrosine kinase) • CARS1 (Cysteinyl-TRNA Synthetase 1)

MET overexpression • MET expression

almost3years

Enhancement of K-Ras Neo-Antigen Targeting CAR-T Cells via Homogenous Knock in of Inducible IL-12 (ASGCT 2023)

Only the complete system of CAR, inducible IL-12, and knock in resulted in complete response without lethal toxicity in all mice receiving the treatment (n=5). This coalesced and modular system has broad applicability for the enhancement of next generation of CAR-T cells targeting solid tumors.

almost 3 years ago

CAR T-Cell Therapy • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • CARS1 (Cysteinyl-TRNA Synthetase 1) • NFATC1 (Nuclear Factor Of Activated T Cells 1)

KRAS G12V

almost3years

Chimeric Antigen Receptor T-cell Therapy in Cancer: A Critical Review. (PubMed, Curr Drug Res Rev)

Given the importance of NK cells in tumor development and metastatic defence, NK cell-based immunotherapies, including adoptive transfer of NK cells, have garnered a lot of interest. With the advancement of improved cellular manufacturing methods, novel cellular engineering strategies, precision genome editing technologies, and combination therapy approaches, we firmly believe that CAR-T cells will soon become an off-the-shelf, cost-effective, and potentially curative therapy for oncogenesis.

almost 3 years ago

Review • Journal • CAR T-Cell Therapy

FLT3 (Fms-related tyrosine kinase 3) • CD276 (CD276 Molecule) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CARS1 (Cysteinyl-TRNA Synthetase 1)

CD123 expression

over3years

Targeted Genomic Insertion of Cars in iPSC-Derived Macrophages Leads to Improved Expression and Anti-Tumor Activity (ASH 2022)

Importantly, these studies also demonstrate that strategies used to genetically modify iPSC-derived cells may need to be modified or optimized depending on which mature cell type of interest is being produced. That is, while randomly integrated CARs seem to work well in iPSC-derived NK cells and T cells, this targeted insertion approach is likely needed for derivation of more functional iPSC-derived CAR-macrophages.

over 3 years ago

IO biomarker

MERTK (MER Proto-Oncogene, Tyrosine Kinase) • CARS1 (Cysteinyl-TRNA Synthetase 1)

almost4years

PRECLINICAL EVALUATION OF ZILOVERTAMAB-BASED ANTI-ROR1 CHIMERIC ANTIGEN RECEPTORS IN NK AND T CELLS (EHA 2022)

Conclusion The zilovertamab-based CAR tested in this study enhances the NK cell response towards ROR1-expressing cancer cells and enables T cells to clear fast-growing cancer cells in an in vivo model. These findings support the development of anti-ROR1 cell therapies for the potential treatment of ROR1-positive hematological malignancies.

almost 4 years ago

Preclinical

IFNG (Interferon, gamma) • CARS1 (Cysteinyl-TRNA Synthetase 1)

ROR1 expression • ROR1 positive

zilovertamab (UC-961)

4years

Integrated, Integral, and Exploratory Biomarkers in the Development of Poly(ADP-Ribose) Polymerase Inhibitors. (PubMed, Cancer J)

Finally, we summarize new strategies for extending the benefit of PARPi therapy toward broader populations of patients through the use of novel biomarkers. Ultimately, design of a composite biomarker test combining multiple mutational signatures or development of a dynamic assay for functional assessments of homologous recombination may help improve the test accuracy for future patient stratification.

4 years ago

Journal • BRCA Biomarker • PARP Biomarker

HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • CARS1 (Cysteinyl-TRNA Synthetase 1)

HRD • DDR • BRCA mutation