CD39+CD103+ selected CD8+ tumor infiltrating lymphocytes for the treatment of solid tumors 3905

Abstract Description CD39+ CD103 + (double positive, DP) CD8+ T cells are primarily found in solid tumors and are enriched for tumor-reactive cells. These cells exhibit an exhausted phenotype characterized by elevated expression of CD39, PD-1, CTLA-4, and TIM-3. By employing a unique isolation and expansion method, DP tumor-infiltrating lymphocytes (TILs) were expanded, creating AGX-148, a selected TIL product for adoptive T cell therapy. AGX-148 contains a high proportion of tumor-reactive T cells with robust anti-tumor activity, capable of migrating to tumor sites, recognizing autologous tumor cells, and driving tumor regression. A Phase 1 clinical trial (NCT05902520) is currently evaluating AGX-148 in adults with metastatic solid tumors who have progressed after standard treatments. Subjects are divided into three cohorts, each receiving high-dose IL-2 for one week post-TIL transfer, followed by low-dose IL-2 for an additional 1, 2, or 3 weeks. To date, no serious adverse events have been reported. Encouragingly, we observed tumor shrinkage, partial responses, and disease stabilization in the treated subjects. T-cell receptor (TCR) sequencing revealed the long-term persistence of T cell clones from AGX-148 drug product in the peripheral blood of patients. These findings highlight AGX-148’s potential as a promising therapeutic option for metastatic solid tumors. Topic Categories Translational and Interventional Immunology (TI)