DIRECT PARENCHYMAL DELIVERY TO ANY ORGAN OR TUMOR VIA NEXT GENERATION ENDOVASCULAR TECHNIQUE – MINIMALLY INVASIVE AND EFFICIENT METHOD FOR TARGETED CELL AND GENE THERAPY

• Published in: CYTOTHERAPY 2024-06, Vol.26 (6), p.S206-S206
• Main Authors: Al-Saadi, J., Waldén, M., Sohlmér, J., Grankvist, R., Friberger, I., Andersson, A., Lövljung, V., Settergren, M., Carlsten, M., Chien, K., Lundberg, J., Witman, N., Holmin, S.
• Format: Article
• Language: English
• Subjects: endovascular; Medicin och hälsovetenskap; modRNA; MSC
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2024.03.411

A fundamental problem for cell/gene/drug delivery is to achieve right location, concentration and time. More specifically, the successful development of cell and gene therapies has been limited to liquid tumors and liver indications, respectively, due to accessibility and/or biodistribution paradigms. We have developed a next generation endovascular platform technology, the Extroducer™, for minimally invasive direct parenchymal delivery to any organ or tumor. After microendovascular navigation using standard equipment, the ultra-small Extroducer™ penetrates the arterial or venous wall for direct access to the organ parenchyma without causing hemorrhage or thrombosis. The device is now FDA-approved for use in abdominal organs. The concept has been developed in large animals to include delivery also to the heart and the CNS via transvenous and trans-arterial approaches. In pig models, we evaluated efficacy and safety for Extroducer™ delivery using clinical standard angiosuite, endovascular- and imaging equipment. Efficacy was demonstrated with histology for cell engraftment, immunohistochemistry and qPCR for viral transduction and ELISA for protein production. Side effects and accuracy of injections were evaluated by PET/MR, SPECT/CT, angiography, histology and biochemistry. Cells of various types, adenovirus-mediated transduction, modRNA and mesenchymal stem cells (MSC) containing modRNA coding for VEGF, was delivered successfully to different organs including, heart, pancreas, kidney, brain and liver. Efficient delivery and biological responses, including cell engraftment were achieved without significant side effects. Interestingly, MSC's electroporated with modRNA-VEGF gave 200 – 500 times higher protein levels in heart and kidney compared to modRNA-VEGF in citrate buffer- or LNP-carrier, respectively. Data for the different payloads and organs will be presented. Endovascular technique has revolutionized medicine. In this report we show that standard micro-endovascular in combination with the Extroducer™ technique can be used for delivery of different payloads, including cells, directly to the organ parenchyma or tumors. This next generation endovascular platform technology thus enables precise and minimally invasive delivery of any therapeutic payload to organs that are difficult or risky to reach by other methods. There will be numerous applications in regenerative medicine and solid tumor oncological treatment strategies.