The ImmunoVerse™

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.

Dr. Robert Vonderheide, a leading physician-scientist and director at the Abramson Cancer Center, dives into the complexities of pancreatic cancer and immunotherapy. He discusses his evolving perspective on cancer treatment, emphasizing the unique challenges of pancreatic tumors, driven by the KRAS oncogene. Vonderheide explores innovative strategies that combine KRAS inhibitors with immunotherapies like CD40 agonists to enhance immune responses. He also highlights the critical need for early detection and the importance of fostering mentorship in the field.

Dr. Patrick Hwu welcomes Dr. Sandra Demaria, Professor of Radiation Oncology and Pathology at Weill Cornell Medicine and a global leader in cancer immunology. Dr. Demaria shares her pioneering research demonstrating how radiotherapy can transform tumors unresponsive to immune checkpoint inhibitors into responsive ones—a discovery that has reshaped cancer treatment strategies worldwide.   Recorded live from the 2025 SITC Annual Meeting, this episode highlights the emerging science shaping the future of immunotherapy, including late-breaking abstracts and press program findings presented at the conference. As the current vice president of SITC, Dr. Demaria discusses the evolving synergy between radiation and immunotherapy, insights from studying the immune microenvironment and the translation of her discoveries into ongoing clinical trials. She also reflects on the collaborative energy that defines SITC and continues to drive the next generation of combination immunotherapies.

Dr. Mario Sznol, a Yale Medicine professor and Cancer Immunology Program co-director, dives into his groundbreaking work in cancer immunotherapy. He shares insights on pioneering high-dose interleukin-2 trials and the evolution of checkpoint inhibitors like anti-PD-1 and anti-CTLA-4. Discover the challenges of managing immune-related toxicities and the promise of breakthroughs in bispecific antibodies and engineered T-cells. With a focus on collaboration and innovation, Sznol emphasizes the powerful impact of immunotherapy on transforming cancer treatment.

Join Dr. Fred Locke, a pioneer in CAR T-cell therapy and Chair at Moffitt Cancer Center, as he shares his journey inspired by his father's battle with lymphoma. He discusses groundbreaking clinical trials ZUMA-1 and ZUMA-7, revealing how CAR T treatments are revolutionizing lymphoma care. Dr. Locke dives into the science behind CAR T technology, survival strategies against solid tumors, and innovative approaches like donor-derived therapies. Plus, learn how diet and exercise may enhance therapy outcomes, paving the way for outpatient care.

Dr. Thomas Gajewski, a renowned tumor immunologist at the University of Chicago, shares groundbreaking insights on 'hot' and 'cold' tumors, revolutionizing immunotherapy. He explains how the tumor microenvironment and patient genetics influence immune responses, and discusses innovative strategies to convert resistant cold tumors into responsive ones. Fascinatingly, he links the gut microbiome to immunotherapy effectiveness, revealing distinct bacterial patterns in patients. Gajewski also touches on mentorship and the role of music in building scientific community.

Dr. Elizabeth Jaffee, a prominent leader in cancer immunotherapy and Deputy Director at Johns Hopkins, shares her inspiring journey into battling pancreatic cancer. She discusses how early KRAS mutations can be targeted with vaccines to potentially prevent cancer recurrence. Dr. Jaffee emphasizes the importance of using AI in identifying high-risk patients and integrating it with genetic data for personalized prevention. She also highlights the promising results of neoadjuvant immunotherapy and the role of KRAS inhibitors in overcoming treatment resistance.

Dr. James Mulé, a leading immunotherapy researcher with three decades at the forefront, joins to reveal the transformative journey of T-cell therapies. He shares how initial skepticism led to pioneering work at the NCI, where he collaborated with legends like Steve Rosenberg. Mulé discusses groundbreaking advances in tumor-infiltrating lymphocytes, their FDA approval, and expanding their application beyond melanoma. He also highlights the potential of engineered immune strategies to tackle challenging cancers like pancreatic cancer, instilling hope in future therapies.

Dr. Phil Greenberg, a leading immunologist at Fred Hutchinson Cancer Center, shares his groundbreaking work on engineered T-cell therapies. He discusses the evolution from early graft-versus-leukemia insights to modern clinical successes. Listeners learn about innovative techniques like rewiring T cells to target tumors and using CRISPR for precise interventions. Greenberg highlights the importance of mentorship in science and advocates for better communication of research to the public. His vision for the future underscores a transformative potential for cancer treatment.

In this illuminating conversation, Dr. Steven A. Rosenberg, the Chief of the Surgery Branch at the National Cancer Institute, shares his pioneering journey in cancer immunotherapy. He discusses his early motivations and the moment he recognized the immune system's potential in battling cancer. Listeners will hear about his groundbreaking work with IL-2, tumor-infiltrating lymphocytes, and CAR-T therapies. Rosenberg also reflects on overcoming skepticism and his vision for the future of immunotherapy, emphasizing the importance of mentorship and persistence.