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A Long-acting Interleukin-7, RhIL-7-hyFc, Enhances CAR-T Cell Expansion, Persistence, and Anti-tumor Activity

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Chimeric antigen receptor (CAR) T cell therapy is a modern adoptive immunotherapy used to treat patients with relapsed/refractory B cell malignancies. However, clinical results showed that CAR-T cells with suboptimal cytotoxicity and reduced persistence could lead to antigen-positive tumor escape and disease relapse. Interleukin-7 is one of the growth factors related to T cell proliferation and survival. rhIL-7-hyFc, a form of interleukin-7 with longer in vivo serum half-life, was demonstrated to improve CAR-T cell expansion, persistence, and anti-tumor efficacy.

Researchers constructed UCAR-T targeting CD19 or CD33 with T cells from healthy human donors. In vitro culture of UCAR-T with the addition of rhIL-7-hyFc could enhance the CAR-T cell expansion and maintain their polyfunctionality. In a preclinical mouse model experiment, rhIL-7-hyFc promotes expansion, persistence, and anti-tumor efficacy of UCAR-T19 cells in CD19+ tumor-bearing NSG mice and immunocompetent mice. Murine UCAR-T cells were also developed and tested in syngeneic mouse models, and rhIL-7-hyFc improved the survival of CD19-positive tumor-bearing mice with prolonged tumor-free times.

Given the pronounced effect of rhIL-7-hyFc on CAR-T cell expansion and efficacy, rhIL-7-hyFc could also reduce the minimum effective dose of CAR-T cells required for activity. They further elucidated the effects of rhIL-7-hyFc on CAR-T cell phenotype using Single-cell RNA sequencing (scRNA-seq) technology, verifying that rhIL-7-hyFc preferentially expands IL7R positive effector memory CAR-T cells.

Structure of rhIL-7-hyFc and CAR19, and the workflow for UCAR-T productionFig.1 Structure of rhIL-7-hyFc and CAR19, and the workflow for UCAR-T production (Kim, 2022)

Creative Biolabs' Services

CAR-T therapy has become a revolution in the area of cancer treatment. Based on up-to-date technology and years of development experience, Creative Biolabs offers one-stop CAR-T therapy development services covering the whole process of CAR-T production. Our high-quality customer service can best fit your technical, program, and budget requirements which can greatly assist your research and preclinical in vitro and in vivo investigation.

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CAR is engineered elaborately with highly specific in redirecting T cells targeting malicious cancer cells via a monoclonal antibody fragment. Creative Biolabs offers various CAR design and construction services, including classical CARs, Smart™ CAR, and other special CARs. Our standard pipeline can support rapid and high-quality CAR production.

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As CAR-T cell production is largely dependent on CAR gene transfer, genetic engineering of T lymphocytes is one of the most critical steps in generating effective CAR-T cells. Creative Biolabs offers CAR gene packaging and delivery services using versatile methods, including lentivirus transfection, electroporation, and transposon-based transfection.

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The development of universal CAR-T from healthy donors could overcome most drawbacks of autologous CAR-T, reducing costs and manufacturing periods. Creative Biolabs offers clients comprehensive solutions to UCAR-T production and insight to overcome the challenges and hurdles in the production process.

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Primary mouse CAR-T is an invaluable tool in testing CAR-T cells' response and function after adoptive transfer in various mouse models. Creative Biolabs has a reliable platform in primary murine CAR-T production, equipped with abundant experience in primary mouse T cell engineering and large-scale and long-term culturing of the transduced cell.

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To obtain high-quality CAR-T cells, in vitro efficacy test is necessary to verify the solid success of CAR-T construction and superior function. Creative Biolabs offers multiple evaluation services, including CAR expression test, cytokines release test, cytotoxicity test, cell proliferation test, viability test, bio-distribution analysis, and efficacy test.

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CAR-T Preclinical In Vivo Assay Services

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Preclinical in vivo therapeutic efficacy tests of CAR-T cells in animal models provide valuable information for their later clinical application. Creative Biolabs offers end-to-end workflows, including choosing animal models, designing comprehensive research practices, and handling high-quality in vivo studies.

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Related Products at Creative Biolabs

Creative Biolabs provides various products and kits covering the whole process of immunotherapy development for multiple cancers and antigen targets, such as CAR vector products, CAR cell products, CAR viral particles, CAR animal cells, and so on. Our products are validated by our in-house scientists with high quality and are recognized by global clients.

Reference

  1. Kim, Miriam Y.; et al. A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR-T cell expansion, persistence, and anti-tumor activity. Nature communications. 2022, 13(1): 3296.
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