Objective:

To summarize recent advancements in CAR T cell therapy and gene therapy approaches targeting various cancers and conditions.

Approach:

• CAR T Design Targets Mesothelin’s “Stump”: Development of CAR 422 targeting a mesothelin stump to improve efficacy in ovarian and pancreatic cancer models.
• Engineered Tregs Suppress Allergic Asthma in Mice: Creation of CAlleR Tregs to reduce allergic asthma symptoms in mouse models.
• Radiopharmaceutical Boosts CAR T in Neuroblastoma Models: Combination of CAR T cells with [67Cu]Cu-LLP2A radiopharmaceutical enhances tumor regression in neuroblastoma.
• Gene Therapy Shows Durable Effect in MMA Mouse Model: Liver-directed lentiviral gene therapy demonstrates long-lasting effects in methylmalonic acidemia mouse models.
• Gene Therapy Platform Targets Human Glia Across the Brain: Development of a gene therapy platform using AAV5 capsids to target human glial cells in the brain.

Key Findings:

• CAR 422 effectively controlled tumor growth in ovarian cancer models with high shed mesothelin.
• CAlleR Tregs reduced allergic inflammation and prevented asthma-like symptoms in mice.
• [67Cu]Cu-LLP2A enhanced CAR T cell activity and reshaped the tumor microenvironment in neuroblastoma.
• Liver-directed gene therapy showed sustained improvement in metabolic disorder features in mice.
• AAV5 gene therapy platform selectively targets human glial cells and enhances delivery through the brain.

Interpretation:

Conclusion: