Polymer- and lipid-based gene delivery technology for CAR T cell therapy

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Polymer- and lipid-based gene delivery technology for CAR T cell therapy

Terça, 04.04.2023

Chimeric antigen receptor (CAR) T cell therapy represents a significant breakthrough in cancer treatment, offering a new approach to enhance the immune system's ability to fight cancer. The therapy involves engineering T cells with synthetic receptors called CARs to recognize and destroy cancer cells. Despite significant advancements in the field, most production of these T cells can be done through viral vectors, which comes with high costs, safety concerns, and production challenges. The nanosystems present an exciting opportunity to overcome these challenges, resulting in a safer and more cost-effective platform for producing CAR T cells. Among them, polymers and lipids have shown great promise for manufacturing various gene delivery platforms for CAR T cell engineering. A recent review published in the Journal of Controlled Release by researchers at the Center for Neuroscience and Cell Biology at the University of Coimbra provides a comprehensive overview of nanosystems as non-viral gene delivery platforms explored for engineering CAR T cells. The researchers highlighted the potential of lipid and polymer-based nanosystems as a prominent technology for T-cell transfection, giving specific examples and applications. Furthermore, they discussed potential approaches to improve T-cell transfection and thus overcome existing challenges before their clinical application. By designing better nanocarriers, the production of CAR T cells can be more cost-effective for a broader range of cancer types. With their continued optimization, the nanocarriers can improve the current T cell-based cancer treatments and lead to the development of next-generation T cell therapeutics.

Inês S. Pinto 1,2 Rosemeyre Cordeiro 1,3 Henrique Faneca 1,3

1. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal

2. Department of Medical Sciences, University of Aveiro, Campus Universitário de Santiago, Agra do Castro, 3810-193 Aveiro, Portugal

3. Institute of Interdisciplinary Research (III), University of Coimbra, Casa Costa Alemão - Pólo II, 3030-789 Coimbra, Portugal

Chimeric antigen receptor T cell (CAR T cell) therapy is a revolutionary approach approved by the FDA and EMA to treat B cell malignancies and multiple myeloma. The production of these T cells has been done through viral vectors, which come with safety concerns, high cost and production challenges, and more recently also through electroporation, which can be extremely cytotoxic. In this context, nanosystems can constitute an alternative to overcome the challenges associated with current methods, resulting in a safe and cost-effective platform. However, the barriers associated with T cells transfection show that the design and engineering of novel approaches in this field are highly imperative. Here, we present an overview from CAR constitution to transfection technologies used in T cells, highlighting the lipid- and polymer-based nanoparticles as a potential delivery platform. Specifically, we provide examples, strengths and weaknesses of nanosystem formulations, and advances in nanoparticle design to improve transfection of T cells. This review will guide the researchers in the design and development of novel nanosystems for next-generation CAR T therapeutics.

Journal of Controlled Release