Pioneering PD-1 Immunotherapy and Tumor-Infiltrating Lymphocytes, ft. Dr. Suzanne Topalian

Dr. Patrick Hwu welcomes Dr. Suzanne Topalian, Bloomberg-Kimmel Professor of Cancer Immunotherapy at Johns Hopkins and Director of the Melanoma Program at the Sidney Kimmel Comprehensive Cancer Center. Dr. Topalian shares her journey from surgical residency to groundbreaking research in tumor-infiltrating lymphocytes (TILs) and immune checkpoint blockade. She discusses the evolution of PD-1 inhibition, her contributions to biomarker discovery, and her work expanding immunotherapy to rare cancers like Merkel cell carcinoma. Dr. Topalian also explores the promise of neoadjuvant immunotherapy, the importance of persistence in research, and the role of mentorship in shaping the next generation of cancer scientists. Throughout the conversation, she emphasizes the collaborative, patient-centered approach that has defined her career and continues to drive advances in cancer immunotherapy.

Key Takeaways

• Immunotherapy translation is a marathon - TIL development required decades from concept to FDA approval. Persistence, infrastructure scaling, and multi-disciplinary collaboration were critical.
  
• Helper T cells and other immune subsets deserve continued focus - early CD4 work opened the door to a broader understanding of immune network contributions beyond cytotoxic T cells.
  
• Checkpoint inhibitors transformed expectations for advanced disease - first-in-human PD-1 trials demonstrated tumor regression in treatment-refractory melanoma, lung, and renal cancers—creating a new standard of care and catalyzing pharmaceutical development.
  
• Neoadjuvant immunotherapy offers biological and clinical advantages - treating tumors in situ may better prime tumor-resident T cells and reduce microscopic metastases before surgical resection.
  
• Manufacturing scale and technological innovation matter - transitioning from wells to bioreactor-type systems enabled effective TIL dosing thresholds and clinical response.