Ep. 129: Live from IMMUNOLOGY2026TM: Emerging Immunotherapies for Solid Tumors

In this live episode from Immunology 2026, hosts Jason Goldsmith and Brenda Roud are joined by Dr. Charles Stentman and Dr. Julia Escobar to explore the frontiers and challenges of immunotherapies for solid tumors. The conversation centers on why CAR T-cell therapies—revolutionary in hematologic cancers—have struggled to translate to solid tumors, with key barriers including poor tumor penetration due to dense stroma, antigen heterogeneity, and immunosuppressive microenvironments. Dr. Escobar highlights innovative strategies like engineering CAR T-cells to release T-cell engagers that degrade stroma and target multiple antigens to prevent escape, while Dr. Stentman discusses the promise of allogeneic and non-T cell therapies such as CAR NK and CAR macrophages, which naturally infiltrate tumors and can be reprogrammed to resist suppression. The discussion also turns to in vivo CAR T-cell manufacturing using lipid nanoparticles and viral vectors, offering a path to bypass complex ex vivo production—but raising new safety concerns like innate immune activation and genotoxicity. The episode concludes with a forward-looking vision: cell therapies expanding beyond oncology into autoimmune diseases, neurodegeneration, and tissue regeneration, enabled by synthetic biology and smart control systems. Key takeaways include: 1) Overcoming solid tumor resistance requires multi-pronged engineering—targeting both tumor cells and the supportive microenvironment; 2) In vivo manufacturing is promising but introduces novel toxicities requiring careful risk assessment; 3) Allogeneic and non-T cell platforms (NK, macrophages) offer 'off-the-shelf' advantages and unique tumor-homing capabilities; 4) The future lies in dynamic, responsive cell therapies that can adapt to changing tumor biology and patient physiology; and 5) Success in solid tumors demands early integration of clinical translation considerations, including GMP compliance, patient fitness, and manufacturing scalability.