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TiCARos Unveils Switchable CAR-T Therapy Demonstrating Enhanced Safety and Efficacy in Solid Tumors

• TiCARos' switchable CAR-T technology overcomes on-target off-tumor toxicity, a major limitation in existing CAR-T therapies, particularly for solid cancers. • The novel approach uses a chemically tagged cotinine adapter to indirectly target cancer cells, sparing normal tissues and reducing toxicity in animal studies. • A suicidal switch mechanism provides an added layer of safety, allowing for the removal of CAR-T cells if necessary, enhancing the therapeutic control. • Human T-cell trials confirmed the efficacy and safety of the switchable CAR-T system, suggesting its potential for treating both solid tumors and hematologic cancers.

TiCARos has announced a breakthrough in CAR-T therapy with its "Switchable CAR-T" technology, offering a potentially safer and more effective approach for treating solid tumors. The research, led by CTO Choi Kyung-ho, a professor of biochemistry at Seoul National University School of Medicine, was published in Nature Communications on November 18.

Overcoming Toxicity Challenges in Solid Tumors

Existing CAR-T therapies have demonstrated remarkable success in hematological cancers. However, their application to solid tumors has been hindered by on-target off-tumor toxicity, which occurs when the target antigen is also expressed in normal cells. This lack of specificity has posed a significant challenge in developing CAR-T therapies for solid cancers.

Innovative Switchable CAR-T System

To address these limitations, the researchers developed a switchable CAR-T system. This system uses a chemically tagged cotinine adapter to enable CAR-T cells to indirectly attack cancer cells. In preclinical animal studies, conventional CD40 CAR-T cells caused severe toxicity to normal tissues, including the lungs and liver. In contrast, the switchable CAR-T system selectively eliminated cancer cells while sparing normal tissues, demonstrating a significant improvement in safety.

Enhanced Safety Measures

As an additional safety measure, the team incorporated a suicidal switch into the adapter. This allows for the removal of CAR-T cells if necessary, providing greater control over potential adverse effects. Human T-cell trials have demonstrated similar efficacy and safety profiles, reinforcing the potential of this technology for treating both solid tumors and hematologic cancers.

Clinical Development and Future Directions

TiCARos is currently conducting phase 1 clinical trials of its TC011 therapy at Seoul National University Hospital and Severance Hospital. The company is also collaborating with Australia's Cartherics to expand its technology into the CAR-NK field. According to a TiCARos official, the switchable CAR-T technology represents an innovative platform that can address the toxicity challenges that have plagued the development of solid cancer therapies, positioning TiCARos competitively in the global market.
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Reference News

[1]
TiCARos unveils breakthrough switchable CAR-T therapy for solid cancers - KBR
koreabiomed.com · Nov 25, 2024

TiCARos' “Switchable CAR-T” technology, developed by Seoul National University and Sungkyunkwan University, was publishe...

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