New Exosome Platform for In Vivo CAR-T

Why it matters

- The shift to an *in vivo* approach aims to circumvent the complex and costly manufacturing process of traditional *ex vivo* CAR-T therapies, which involves extracting a patient's T-cells, engineering them in a lab, and then re-infusing them. This could transition CAR-T from a highly individualized treatment to a more accessible, "off-the-shelf" therapy. - Using exosomes as a delivery vehicle is a key feature of the EXO 001 platform; these nanoscale vesicles can carry the CAR machinery and may offer better tissue penetration into solid tumors and a lower risk of toxicities like cytokine release syndrome (CRS) compared to live cell therapies. - Solid tumors, which account for about 90% of all cancer cases, present significant challenges for traditional CAR-T therapies due to an immunosuppressive tumor microenvironment and antigen heterogeneity. A multi-target approach, as enabled by this platform, is a strategy to prevent tumor escape. - The developer, Ever Supreme Bio Technology, has a separate allogeneic (off-the-shelf) CAR-T product, CAR001, in Phase I/IIa clinical trials for solid tumors. That therapy targets HLA-G and PD-L1 and utilizes a non-viral mRNA modification method, indicating the company's experience in non-viral gene delivery and multi-target cell therapy. - The collaboration is built on existing research from China Medical University Hospital, where Superintendent Der-Yang Cho's team has previously published on using CAR-NK (Natural Killer) cells to target HLA-G in various solid tumors. - *In vivo* generation of CAR-T cells bypasses the need for lymphodepletion, a harsh chemotherapy regimen required to make space for *ex vivo* manufactured cells, which could make the therapy suitable for a wider range of patients and earlier lines of treatment. - The development of non-viral gene delivery platforms is a major industry trend aimed at reducing the costs and regulatory complexities associated with the viral vectors (like lentiviruses) commonly used in first-generation CAR-T products.

Key numbers

• Researchers at China Medical University Hospital and Ever Supreme Bio Technology have developed the EXO 001 exosome platform, designed to enable in vivo multi-target CAR-T therapy for solid tumors.
• Solid tumors, which account for about 90% of all cancer cases, present significant challenges for traditional CAR-T therapies due to an immunosuppressive tumor microenvironment and antigen heterogeneity.
• The developer, Ever Supreme Bio Technology, has a separate allogeneic (off-the-shelf) CAR-T product, CAR001, in Phase I/IIa clinical trials for solid tumors.
• That therapy targets HLA-G and PD-L1 and utilizes a non-viral mRNA modification method, indicating the company's experience in non-viral gene delivery and multi-target cell therapy.

What happens next

• The shift to an *in vivo* approach aims to circumvent the complex and costly manufacturing process of traditional *ex vivo* CAR-T therapies, which involves extracting a patient's T-cells, engineering them in a lab, and then re-infusing them.
• This could transition CAR-T from a highly individualized treatment to a more accessible, "off-the-shelf" therapy.
• A multi-target approach, as enabled by this platform, is a strategy to prevent tumor escape.

Sources

• have developed
• The shift to an *in
• Using exosomes as a
• Solid tumors, which
• A multi-target approach
• The developer, Ever
• The collaboration is
• The development of

Quick answers