Implantable CAR T cell factories enhance solid tumor treatment

<h3>Background & Aim</h3> Chimeric Antigen Receptor (CAR) T cell therapy has produced revolutionary success in hematological cancers such as leukemia and lymphoma. Nonetheless, its translation to solid tumors faces challenges due to manufacturing complexities, short-lived in vivo persistence, and transient therapeutic impact. Here, we introduce 'Drydux' - an innovative macroporous biomaterial scaffold platform designed for rapid, efficient in-situ generation of tumor-specific CAR T cells. Drydux expedites CAR T cell manufacturing with a mere three-day turnaround from patient blood collection, presenting a cost-effective, streamlined alternative to conventional methodologies. <h3>Methodology</h3> Macroporous biomaterial scaffold platform was used to generate CAR T cells targeting various solid tumors. Within 3 days of T cell isolation from blood, activated T cells along with CAR encoding retrovirus was seeded onto a scaffold and implanted in a tumor bearing mice. Animals were monitored for tumor regression using bioluminescence imaging and blood assessment was done periodically to monitor CAR T cell persistence post treatment. <h3>Results</h3> Drydux-enabled CAR T cells provided prolonged in vivo release, functionality, and enhanced persistence in solid tumor models, with cells showing less differentiated to memory phenotypes. Unlike conventional CAR T cell therapy, which offered only temporary tumor control, equivalent Drydux cell doses induced lasting tumor remission in various animal tumor models, including systemic lymphoma, peritoneal ovarian cancer, metastatic lung cancer, and orthotopic pancreatic cancer. <h3>Conclusion</h3> Drydux's approach holds promise in revolutionizing solid tumor CAR T cell therapy by delivering durable, rapid, and cost-effective treatments and broadening patient accessibility to this groundbreaking therapy.