By Fineline Cube China-based chimeric antigen receptor (CAR)-T cell specialist CARsgen Therapeutics Holdings Ltd (HKG: 2171) has announced the development of a new therapeutic technique in collaboration with the Shanghai Cancer Institute (SCI) that significantly increases the anti-solid tumor activity of T cells. Their findings were published in the journal Molecular Therapy.
Study Background and Findings
Limited T cell persistence is a major challenge in CAR-T cell therapy for solid tumors. While engineering T cells to secrete proinflammatory cytokines has been explored to improve persistence, other methods remain understudied. Runx3, a master regulator of T cell development and differentiation, has been shown to promote T-cell persistence in solid tumors through a transgenic mouse model study. CARsgen researchers generated CAR-T cells overexpressing Runx3 (Run-CAR-T cells) and found that these cells exhibited long-lasting antitumor activities and achieved better tumor control than conventional CAR-T cells.
Mechanism and Clinical Implications
The study observed that more Run-CAR-T cells circulated in the peripheral blood and accumulated in tumor tissue, indicating that Runx3 co-expression improved CAR-T cell persistence in vivo. Tumor-infiltrating Run-CAR-T cells showed less cell death with enhanced proliferative and effector activities. In vitro studies also indicated that activation-induced cell death (AICD) was decreased in Run-CAR-T cells via downregulation of tumor necrosis factor (TNF) secretion. Further research revealed that Runx3 could bind to the TNF promoter and suppress its gene transcription after T cell activation. These findings suggest that Runx3-armored CAR-T cells could be a new modality for treating solid tumors, offering increased antitumor activities.
Future Prospects and Strategic Implications
The development of this new therapeutic technique marks a significant advancement in CAR-T therapy, positioning CARsgen Therapeutics at the forefront of innovation in oncology. By enhancing the persistence and efficacy of CAR-T cells, this approach has the potential to address significant unmet medical needs in the treatment of solid tumors, improving patient outcomes and quality of life.-Fineline Info & Tech