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Solid tumors are more refractory to chimeric antigen receptor (CAR) T-cell immunotherapies compared with hematological malignancy. Effector T-cell function was reduced in the tumor microenvironment, including accessibility, expansion, and persistent cytotoxicity.
A new study led by Kyoto University researchers published in Nature has documented the methods of generating CAR-T cells in CD8 type derived from iPSCs, which have the potential to improve efficacy in a solid tumor. They discovered that 1928bbz-based third-generation CARs efficiently increased cell differentiation into CD4CD8 double-positive cells by transducing CAR constructs into T-iPSC line-derived hematopoietic progenitor cells. Following that, immature CD4CD8 DP iCAR-T cells are activated by an anti-CD3 antibody to induce CD8 SP cells.
They created an iPSC-derived CD8αβ cytotoxic CAR-T that was targeted to GPC3, a hepatocellular carcinoma-specific membrane protein, in the study. T-cell activation signal pathways were genomically edited in this product to improve iCAR-TCTL therapeutic efficacy. At the iPSC stage, Diacylglycerol (DAG) metabolism-related kinase, DGKα, and DGKζ were double knocked out. In addition, mbIL-15 and IL-15Rα were expressed in iCAR-TCTL. The FCM analysis of surface molecules revealed that the cells are memory T-cells. Using advanced principal component analysis and hierarchical clustering analysis, scientists discovered an improvement in CD3ζ-mediated T cell activation, allowing iCAR-T cell proliferation in the tumor. IL-15 increased memory-related marker expression while decreasing exhaustion-related marker expression.
In a liver cancer subcutaneous xenograft mouse model, the in vivo therapeutic efficacy of genetically manipulated iCAR-T cells was tested. The combined expression of DGK-dKO and mbIL-15 on iCAR-TCTL has an effective anti-tumor function for solid tumors and improves cell proliferation and persistence when compared to primary CD8+ CAR-T cells.
Fig.1 Combination of DGK-dKO and mbIL15 expression enhanced iCAR-TCTL anti-tumour function. (Tatsuki Ueda, 2022)
CD8αβ cytotoxic iCAR-T cells derived from iPSCs have the potential to improve the cancer immunity of CAR-T-cell therapies. Creative Biolabs, the leading immunotherapeutic biotech that provides cell therapy-related services, provides one-stop CAR-T cell production using iPSC technology as well as comprehensive cell analysis services for therapeutic efficacy tests.
CAR-T hailed as "a living drug" is an excellent immunotherapy for cancer treatment. Creative Biolabs offers highly specific CARs from first- to third-generation and designs special CARs to improve T cell survival in the tumor environment. Please contact us to learn more CAR design and construction services.
CAR constructs delivered via retrovirus or lentivirus face a problem of random insertion into the genomes of recipient T cells, which can result in unexpected side effects. Creative Biolabs has extensive experience with CRISPR-based genome editing. We have created several novel approaches to combining CRISPR and CAR therapy.
To overcome the limitations of autologous CAR-T cells, various strategies are being used to develop "off-the-shelf" CAR T-cell therapies. CAR-iT cells derived from induced pluripotent stem cells are available from Creative Biolabs (iPSCs). CAR is transduced into iPSCs and then differentiated into mature T cells.
The in vivo evaluation of CAR-T cells in animal models is critical for researchers. In vivo data on tumor recognition and killing is valuable for CAR-T optimization. Creative Biolabs has created an innovative CellRapeutics™ platform with a variety of robust animal models to provide clients with safety and efficacy assays.
The degree of cellular homogeneity within tumor tissues influences the efficacy of CAR-T therapies. Single-cell sequencing services are provided by Creative Biolabs to analyze genetic polymorphisms in thousands of single cells. SCS, when combined with our CAR platform, allows us to provide more precise information about CAR-T to our clients.
Natural killer (NK) cells are lymphocytes that function as part of the innate immune system. Human pluripotent stem cells can now be used to generate NK cells (PSC). We developed the one-stop CAR-NK platform at Creative Biolabs, which includes using iPSC technology to generate NK cells derived from CAR-expressing stem cells and a CRISPR/Cas9-based iPSC-NK cell editing platform.
Creative Biolabs is a well-known cell therapeutic biotech providing cell therapy-related services and products. Our products and reagents cover every process of immunotherapy development for multiple cancers and antigen targets, such as lentiviral and retroviral vectors and packaging kits, CAR-engineered T cells of specific subtypes, and so on. Please browse the following products to find the right product for your project.
CD19-Targeted Product Category | GPC3-Targeted Product Category |
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