CAR-T Cell Therapy

Non-viral CAR-T Therapies for Blood Cancers

Alaunos is advancing Sleeping Beauty transposition, one of the most clinically advanced non-viral cell therapy technologies, to develop therapeutics for both solid tumors and blood cancers. For malignancies like myeloma, leukemia and lymphoma, CD19 and B-cell maturation antigen (BCMA) are the most attractive targets for CAR-T cell therapy because they are highly expressed on the cancer cell surface and are critical for the survival of the cancer.

Sleeping Beauty is a transposon/transposase system that uses DNA plasmids to reprogram T-cell DNA. Sleeping Beauty-modified CAR-T cells have been administered to patients and demonstrated safety, tolerability, disease response, long-term survival, and persistence of infused CD19-specific CAR+ T-cells. Following the original Phase 1 CAR-T clinical studies using Sleeping Beauty, Alaunos has further advanced the technology. Alaunos’ bioengineering approach for CAR-T has three components:

First, using a CAR we program T cells to attack CD19, a known antigen on the surface of malignant B cells (leukemia/lymphoma) or BCMA on the surface of plasma cells (myeloma).
Second, we tether interleukin 15 to the T-cells’ membranes, and this membrane-bound IL-15 or mbIL-15 is designed to give the T-cells a survival advantage and stave off immune cell exhaustion so the T-cells can kill and continue to kill cancer cells.
Third, we insert a molecular safety switch into the DNA, letting us eliminate the modified T cells as needed.

The Process Reduces Time to Treatment

Our Sleeping Beauty system greatly reduces the time between genetic modification and infusion, making it possible to manufacture T cells on site where patients are receiving their care. Other viral-based CAR-T cell therapies take weeks to manufacture and are generally produced in centralized manufacturing facilities.

Under our rapid personalized manufacturing (RPM) approach, genetically modified CAR-T cells are rapidly manufactured in autologous cells onsite in less than two days following gene transfer.

Leukemia and lymphoma patients with CD19+ disease have been infused with CAR-T cells manufactured by RPM.

Alaunos is seeking a partner for its CD19 and BCMA CAR-T assets to continue clinical development.