The approval of lifileucel in 2024 marked an important milestone in oncology as the first cellular therapy authorized for a solid tumor. This milestone stands in sharp contrast to the success of CAR-T cells in hematologic malignancies, where six products have been licensed, and highlights the central challenge that solid tumors remain largely unconquered. At the mechanistic core lies a three-stage framework describing the major barriers encountered by therapeutic T cells in solid tumors, a series of escalating barriers that any therapeutic T cell must overcome to achieve durable tumor control: (1) Access: overcoming stromal and vascular barriers that restrict T-cell infiltration into tumors, (2) Recognition: identifying malignant cells in the setting of antigen heterogeneity and immune evasion, and (3) Persistence: maintaining T-cell function within the immunosuppressive tumor microenvironment. Historically, CAR-T and TIL therapies were viewed in competition, each occupying distinct niches. The field is increasingly adopting a convergent paradigm in which both platforms address a common challenge: overcoming the biological barriers that limit durable responses in solid tumors through complementary engineering and biological strategies. We review the biological obstacles, emerging convergence strategies, and translational frameworks including biomarker-guided patient selection that define this new area. Therapeutic selection may increasingly be guided by a tumor’s dominant biological barriers rather than by platform classification alone.
Duc-Hiep Bach, Van T. Hoang, T. Pham et al.· Cancer Cell International· 1 citation
Regenerative medicine, characterized by breakthroughs in stem cell technology, cell-free therapies, and tissue engineering, holds immense promise for treating various diseases. However, along with the encouraging advancements in translational and clinical research, emerging evidence has demonstrated a potential risk of developing instant blood-mediated inflammatory reactions (IBMIRs) and venous thromboembolism (VTE) with the intravascular delivery of cellular products that do not naturally come into contact with blood. Tissue factor (TF), an initiator of the extrinsic coagulation cascade, plays a pivotal role in these processes. In this comprehensive review, we summarize the biological properties and multifaceted functions of TF in both health and disease. By understanding its physiological and pathological roles, we discuss the implications of TF for IBMIR and VTE in patients receiving cell therapy and extracellular vesicle (EV) therapy. VTEs, including deep vein thrombosis and pulmonary embolism, might have life-threatening consequences. During IBMIR, the recipient’s innate immune cells and humoral coagulation factors drive a hyperacute thromboinflammatory response that traps the infused products, leading to rapid intravascular clearance and compromised therapeutic outcomes. Additionally, we introduce transplantation protocols that demonstrate prevention and monitoring strategies for TF-induced negative effects. Given the increasing complexity of clinical studies and the diverse applications of cell-based therapies, mitigating TF-induced thrombosis is crucial for safer and more effective treatments.
Van T. Hoang, Quyen Thi Nguyen, D. Le et al.· Frontiers in Cell and Develo...· 0 citations
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