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Organoid-induced Differentiation of Conventional T Cells from hPSCs

As a world leader in CAR-T services, Creative Biolabs is dedicated to exploring more innovative and cutting-edge technologies to accelerate CAR-T discovery and development. Our scientists have extensive expertise in the field of CAR-T, and also stem cells to ensure strong knowledge basics. Both the experienced team and advanced platform enable us to provide comprehensive services to our clients in a diverse range.

Our Inspiration

CAR-T cell therapy has shown great efficacy in the treatment of hematological malignancies and even solid tumors and chronic viral infections, thus considering to be one of the most promising cancer immunotherapies. While some limitations need to be improved for making common CAR-T cells. For conventional CAR-T cell therapy, it’s very expensive since it’s specific for the patients. T cell is derived from the patients and then engineered to become CAR-T cell which will be injected back into the patient (see Fig.1). Hence, exploring novel strategies to generate conventional naïve T cells is meaningful to facilitate universal, off-the-shelf CAR-T cell products.

Treatment of patients with B-cell malignancies using anti-CD19 CAR T cells.

Fig.1 Treatment of patients with B-cell malignancies using anti-CD19 CAR T cells. (Klebanoff, 2014)

Organoid-Induced Differentiation of Conventional T Cells From Human Pluripotent Stem Cells

Based on the reported method to generate conventional T cells from human pluripotent stem cells (see Fig.2), our scientists are dedicated to establishing this platform which enables the potential to transform autologous T cell immunotherapy to universal, off-the-shelf cell products. We established the pluripotent stem cell (PSC)-artificial thymic organoid system to generate mature, functional T cells from human PSCs. We used this system to successfully generate naive CD3+CD8αβ+ and CD3+CD4+ conventional T cells with a diverse T cell receptor (TCR) repertoire. When an MHC class I-restricted TCR was introduced in PSCs, naïve and antigen-specific CD8αβ+ T cells can be produced. For this kind of CD8 T cells, there is no endogenous TCR expression, and they showed anti-tumor activity both in vitro and in vivo. This characterization ensures the generated T cells are functional and can be used for universal, off-the-shelf CAR-T cell products.

Organoid-Induced Differentiation of Conventional T Cells from Human Pluripotent Stem Cells.

Fig.2 Organoid-Induced Differentiation of Conventional T Cells from Human Pluripotent Stem Cells. (Montel-Hagen A, 2019)

Highlights

This method is an efficient and standardized organoid system which can induce hematopoietic specification and conventional naïve T cell generation. Also, it enables the generation of naïve, antigen-specific T cells which hold anti-tumor activity.

  • PSC derived conventional T cells are transcriptionally similar to primary conventional T cells,
  • TCR-engineered PSCs in organoids can generate naïve, antigen-specific T cells.

Why choose Creative Biolabs

  • Advanced platform and senior scientists,
  • Short turnaround time with competitive price,
  • Collaboration between scientists across various areas,
  • Fully end-to-end solution provider.

This platform had been validated by our scientists via T cell in vitro and in vivo functional assays. Creative Biolabs is dedicated to advancing your CAR-T projects with versatile systems. We are committed to providing the most valuable and innovative solutions to our clients to facilitate your CAR-T projects. Our innovative and collaborative approach enables us to offer a broad range of services. If you are interested in any CAR-T related technologies, please feel free to contact us to learn how we can be involved in your projects.

References

  1. Harris, D.T, and Kranz, D.M, Adoptive T Cell Therapies: A Comparison of T Cell Receptors and Chimeric Antigen Receptors. Trends Pharmacol Sci. 2016, Mar;37(3): 220-230.
  2. Montel-Hagen, Amélie, et al. "Organoid-induced differentiation of conventional T cells from human pluripotent stem cells." Cell stem cell (2019).

Online Inquiry

For any technical issues or products/services related questions, please leave your contacts as below, and our team will contact you at earliest convenience to let you know how we can be involved in your projects.

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