New Majestic solution for future cancer cell therapies

A new gene delivery and immune cell engineering technology.

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Utilizing a patient’s immune system, adoptive cell therapy (ACT), also known as cellular immunotherapy, treats conditions including cancer.

Transferring these “living drugs” through CAR T-cell therapy has significantly improved clinical efficacy in targeting and eliminating tumor cells by genetically changing immunological T cells in a lab.

Cell therapy production, research, and development depend on immune cell engineering, and most CAR-T cells produced today for clinical trials are made using lentiviral or retroviral systems. However, these sources have drawbacks because they are relatively safe to produce, have a limited lifespan, and can have a higher risk of cellular toxicity.

Scientists at Yale have developed a new gene delivery and immune cell engineering technology with the potential to advance cell therapies for cancer and other diseases. They have developed a new gene delivery system to produce a superior cell engineering system called MAJESTIC (mRNA AAV-Sleeping-Beauty Joint Engineering of Stable Therapeutic Immune Cells).

Besides being an organic combination of gene delivery approaches like mRNA, transposon, and adeno-associated virus (AAV), the new system outperforms existing gene delivery platforms for cell therapy.

The researchers demonstrate how the new approach safely generates CAR-T cells and other therapeutic immune cells by delivering transgenes into human immune cells and other cell types with improved efficiency, decreased cellular toxicity, and stable transgene expression.

The MAJESTIC system’s adaptability offers benefits that might encourage the FDA to approve more immune cell-based therapies for treating cancer and other disorders.

Journal Reference:

  1. Ye, L., Lam, S.Z., Yang, L. et al. AAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells. Nat. Biomed. Eng (2023). DOI: 10.1038/s41551-023-01058-6
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