177 - The development of cancer immunotherapy and its promise for treating advanced cancers

The Peter Attia Drive Podcast

27 Sept 2021131:34

EducationalLearning

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TLDRIn this profound conversation, Dr. Peter Attia hosts Dr. Steven Rosenberg, a pioneering figure in cancer immunotherapy. Dr. Rosenberg shares his chronological journey, beginning with his early fascination with science sparked by personal tragedy, through to his groundbreaking contributions to the field of oncology. He discusses the trials, tribulations, and triumphs of developing effective immunotherapies, including IL-2 therapy, tumor-infiltrating lymphocytes (TIL), and the revolutionary CAR T-cell therapy. Rosenberg's narrative is a testament to the relentless pursuit of medical advancements to combat cancer, underscored by personal anecdotes, reflections on patient care, and a vision for the future of cancer treatment.

Takeaways

🔬 Dr. Rosenberg is a pioneering figure in cancer immunotherapy, dedicating his career to developing treatments to alleviate and cure cancer.
🧬 The journey to discover effective cancer treatments is marked by incremental advancements, starting from high-dose IL-2 to the exploration of genetically modified T cells.
👨‍🔬 Rosenberg's work highlights the importance of perseverance in medical research, navigating through numerous patient trials and setbacks to achieve breakthroughs.
💡 The concept of tumor-infiltrating lymphocytes (TILs) and genetically modifying T cells to recognize cancer-specific antigens represents a significant leap forward in cancer treatment.
🎓 The narrative underscores the critical role of continuous learning, intuition, and adaptation in advancing scientific research and application.
🤝 Collaboration and open sharing of knowledge are emphasized as vital for accelerating progress in cancer treatment research.
🧪 The discovery of checkpoint inhibitors (anti-CTLA-4 and anti-PD-1) marks a pivotal moment in cancer immunotherapy, offering new hope for patients with specific cancer types.
🔎 Rosenberg's research points towards the potential of targeting unique cancer mutations through adoptive cell therapy as the next frontier in cancer treatment.
🙏 The story reflects the emotional and ethical challenges faced by oncologists and researchers in dealing with patient care and the pursuit of groundbreaking treatments.
🌟 The dedication to making a difference in the lives of cancer patients drives relentless pursuit of knowledge and innovation in cancer therapy.

Q & A

What inspired Dr. Rosenberg to become focused on cancer research?
-Dr. Rosenberg's inspiration to focus on cancer research came from his childhood, particularly the impact of learning about the horrors of the Holocaust and his desire to alleviate suffering rather than cause it.
Why did Dr. Rosenberg choose to pursue a PhD in biophysics?
-Dr. Rosenberg pursued a PhD in biophysics to acquire a broad background in the sciences, ensuring he could tackle any problem with confidence and not feel intimidated by what he did not know.
What was the significant moment in Dr. Rosenberg's training that altered the course of his career?
-A significant moment was when Dr. Rosenberg encountered a patient who had undergone a spontaneous regression of cancer, which intrigued him about the potential role of the immune system in cancer treatment.
What led Dr. Rosenberg to work at the National Cancer Institute (NCI)?
-Dr. Rosenberg was drawn to work at the NCI due to its resources, commitment to making progress, and the opportunity to not just practice today's medicine but to create the medicine of tomorrow.
How did Dr. Rosenberg's approach to treating cancer evolve over time?
-Dr. Rosenberg's approach evolved from using high-dose interleukin-2 to stimulate immune responses in cancer patients to the development of adoptive cell transfer therapies, including the engineering of T-cells to target specific cancer cells.
What was the first cancer type where Dr. Rosenberg saw a reproducible regression using immunotherapy?
-The first cancer type where Dr. Rosenberg observed a reproducible regression using immunotherapy was melanoma, following the administration of high-dose interleukin-2.
Why does Dr. Rosenberg believe in the potential of immunotherapy for treating cancer?
-Dr. Rosenberg believes in the potential of immunotherapy because it leverages the body's immune system to recognize and attack cancer cells, offering a highly selective and potent treatment method.
What challenges did Dr. Rosenberg face in the early days of cancer immunotherapy research?
-Dr. Rosenberg faced significant challenges, including skepticism from the scientific community, technical limitations in growing and modifying immune cells, and the emotional toll of treating patients who often did not survive.
How did Dr. Rosenberg contribute to the development of CAR T-cell therapy?
-Dr. Rosenberg contributed to the development of CAR T-cell therapy by experimenting with genetic modifications of T-cells, leading to the creation of chimeric antigen receptors (CARs) that target specific cancer cells.
What is Dr. Rosenberg's vision for the future of cancer treatment?
-Dr. Rosenberg envisions a future where cancer treatment is highly personalized, utilizing the patient's immune system and genetic modifications to target and eradicate cancer cells with precision.

Outlines

00:00

🎙️ Introduction to the Drive Podcast with Dr. Rosenberg

This paragraph introduces the episode of the Drive podcast, where the host, Peter Attia, welcomes Dr. Rosenberg, acknowledging his hard work and dedication to his field. Peter expresses his admiration for Dr. Rosenberg's focus and determination, which started from a young age. The conversation is set to explore Dr. Rosenberg's life story, beginning with his childhood in the Bronx and his early inclination towards science and medicine, sparked by a combination of personal interests and historical events affecting his family during World War II.

05:00

📚 Dr. Rosenberg's Early Years and Academic Journey

Dr. Rosenberg reflects on his early years growing up in the Bronx, highlighting his initial dream of becoming a cowboy before shifting towards a deep-rooted interest in science and medicine. This shift was partly due to the impact of learning about the Holocaust's atrocities, which instilled in him a desire to alleviate suffering through medicine and research. He talks about his education, from excelling in high school to attending medical school through a combined bachelor's and MD program, and the influence of his time at Hopkins in shaping his future in medical research.

10:03

🔬 Inspirational Patients and Path to Immunology

Dr. Rosenberg shares two pivotal patient encounters early in his career that profoundly influenced his path towards cancer research and immunotherapy. The first case involved a patient with spontaneous cancer regression, which sparked Rosenberg's interest in the potential of the immune system to fight cancer. The second case was a kidney transplant patient who developed and then overcame cancer after the cessation of immunosuppressive drugs, further indicating the immune system's role in cancer control. These experiences led Rosenberg to focus on immunology and the potential of the immune system in cancer treatment.

15:06

🧬 Initial Steps in Cancer Immunotherapy

This paragraph details Dr. Rosenberg's initial forays into cancer immunotherapy, starting with his innovative yet ultimately unsuccessful experiment using lymphocytes from pigs to treat cancer patients. Despite the setbacks, the discovery of T-cell growth factor (Interleukin-2) by other researchers opened new avenues for Rosenberg's work, allowing for the growth and manipulation of lymphocytes outside the body, marking the beginning of a series of experiments aimed at utilizing the immune system to fight cancer.

20:09

🏥 From Residency to Leading NCI's Surgery Branch

Dr. Rosenberg narrates his journey from completing his residency to becoming the chief of the Surgery Branch at the National Cancer Institute (NCI) in 1974, a position he still holds. He chose NCI over other prestigious offers due to its resources and mandate to create the medicine of tomorrow. This decision was driven by his lifelong commitment to cancer research, influenced by his childhood experiences and a deep-seated desire to combat the suffering caused by cancer.

25:11

🔎 The Early Days of Cancer Immunotherapy Research

This paragraph explores the challenges and breakthroughs in Dr. Rosenberg's early cancer immunotherapy research. Despite numerous unsuccessful attempts and the death of many patients, a significant turning point came with a patient showing tumor regression after Interleukin-2 treatment in 1984. This milestone validated the potential of immunotherapy in cancer treatment, motivating further exploration into how the immune system could be leveraged to combat cancer.

30:13

📈 Progress and Setbacks in Immunotherapy

Dr. Rosenberg discusses the rollercoaster journey of cancer immunotherapy research, marked by slow progress, setbacks, and moments of breakthrough. He emphasizes the importance of perseverance and intuition in science, highlighting the critical discovery that Interleukin-2 could mediate tumor regression in certain cancers. This discovery was a beacon of hope and set the stage for more focused research on manipulating the immune system to fight cancer.

35:15

🧪 The Evolution of Cancer Immunotherapy

The narrative progresses to detail how Dr. Rosenberg and his team continued to refine their approach to immunotherapy, from the first successful use of Interleukin-2 in treating a patient with melanoma to exploring genetically modified T cells. These efforts were part of a broader endeavor to understand and enhance the immune system's ability to target cancer, leading to groundbreaking treatments such as CAR T-cell therapy for certain blood cancers.

40:16

🌐 Expanding Immunotherapy to Solid Tumors

Dr. Rosenberg shares insights into the ongoing challenge of extending the success of immunotherapy from hematologic cancers to solid tumors. Despite the groundbreaking success of CAR T-cell therapy in treating blood cancers, finding unique cell surface molecules exclusive to solid tumors has been difficult. The conversation underscores the complexity of treating solid tumors and the ongoing search for effective immunotherapy strategies.

45:16

🚀 The Future of Personalized Cancer Immunotherapy

In this concluding paragraph, Dr. Rosenberg expresses optimism about the future of cancer immunotherapy, particularly the potential for personalized treatments targeting unique mutations in solid tumors. He highlights recent advancements in identifying and targeting these mutations, suggesting a promising path forward for developing more effective immunotherapies for a broader range of cancers. This vision for the future represents the culmination of decades of research and the potential for significant breakthroughs in cancer treatment.

Mindmap

Keywords

💡Immunotherapy

Immunotherapy refers to treatments that use the body's immune system to fight diseases, including cancer. In the context of the video, immunotherapy is a central theme, as Dr. Rosenberg discusses his pioneering work in developing treatments that harness the immune system to target and eliminate cancer cells. Examples include the use of interleukin-2 (IL-2) to stimulate the immune system, the development of tumor-infiltrating lymphocytes (TILs) therapies, and the innovation behind chimeric antigen receptor (CAR) T-cell therapy.

💡Tumor-infiltrating lymphocytes (TILs)

Tumor-infiltrating lymphocytes are immune cells that have migrated from the bloodstream into a tumor. They play a crucial role in the body's natural defense against cancer. In the video, Dr. Rosenberg describes how extracting, expanding, and re-infusing TILs back into patients has been a significant part of his research, leading to remarkable responses in some cancer patients by directly attacking the cancer cells with the patient's own immune system.

💡CAR T-cell therapy

CAR T-cell therapy is a form of immunotherapy where a patient's T cells are genetically modified to produce chimeric antigen receptors (CARs) on their surface. These receptors enable the T cells to recognize and attack cancer cells. The video highlights this breakthrough, particularly in treating blood cancers like lymphoma, as a testament to the potential of genetically engineered immune cells in curing cancer.

💡Checkpoint inhibitors

Checkpoint inhibitors are drugs that block immune checkpoints, which are molecules on immune cells that need to be activated (or inhibited) to start an immune response. Cancer cells often use these checkpoints to avoid being attacked by the immune system. Dr. Rosenberg discusses the use of checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4, as a way to unleash the immune system on cancer cells, allowing for the treatment of cancers previously deemed untreatable by other means.

💡Interleukin-2 (IL-2)

Interleukin-2 is a cytokine, a type of protein important for regulating the immune system. It was one of the first cytokines used to boost the immune response against cancer. Dr. Rosenberg recounts his early work with IL-2, highlighting its role in stimulating the growth and activity of immune cells, such as T cells and natural killer cells, to fight cancer.

💡Mutation-specific targeting

Mutation-specific targeting involves identifying and attacking cancer cells based on unique mutations in their DNA. This concept is pivotal in Dr. Rosenberg's discussion about the future of cancer treatment, emphasizing the importance of targeting the unique mutations within a tumor to personalize therapy. This approach underscores the potential for highly specific and effective treatments by exploiting the genetic differences between cancer cells and normal cells.

💡Neoantigens

Neoantigens are new antigens that arise from the mutations in a tumor's DNA that are not present in normal cells. These tumor-specific antigens can be recognized by the immune system. Dr. Rosenberg explains how targeting neoantigens with immunotherapies can lead to effective cancer treatments, as these antigens provide a way for the immune system to distinguish between cancer cells and healthy cells.

💡Gene therapy

Gene therapy involves modifying or manipulating the expression of a gene to treat a disease. In the video, Dr. Rosenberg discusses the use of gene therapy to enhance the effectiveness of immune cells against cancer, including the introduction of genes into T cells to make them more effective at recognizing and killing cancer cells. This approach marks a significant advancement in the ability to tailor immunotherapies to individual patients.

💡Adoptive cell transfer

Adoptive cell transfer is a type of immunotherapy that involves collecting and using patients' own immune cells to treat their cancer. Dr. Rosenberg outlines how this technique, particularly using TILs, has been a cornerstone of his research. By expanding these cells outside the body and reintroducing them into the patient, the immune system's ability to fight cancer is significantly enhanced.

💡HLA molecules

HLA (human leukocyte antigen) molecules play a critical role in the immune system's ability to recognize foreign substances. Dr. Rosenberg discusses the importance of HLA molecules in the context of mutation-specific targeting, explaining how cancer cell mutations need to fit onto a patient's HLA molecules to be recognized by T cells. This compatibility is crucial for the effectiveness of T cell-based therapies, emphasizing the personalized nature of cancer immunotherapy.

Highlights

Dr. Rosenberg's early inspiration to become a doctor stemmed from witnessing the horrors of the Holocaust and a desire to alleviate suffering.

A pivotal moment in Dr. Rosenberg's career was influenced by a patient's spontaneous regression of cancer, sparking interest in the immune system's potential to fight cancer.

The discovery of T-cell growth factor (interleukin-2) opened new doors for manipulating lymphocytes outside the body, marking a significant advancement in immunotherapy.

Dr. Rosenberg's perseverance through numerous patient trials without success, leading to the breakthrough with interleukin-2 and the first patient showing tumor regression.

The operation on President Reagan for colon cancer and the ensuing controversy over publicly acknowledging the diagnosis.

Introduction of gene therapy into clinical practice by inserting a marker gene into patients' lymphocytes, paving the way for genetically modified cell therapies.

The establishment of tumor-infiltrating lymphocytes (TIL) therapy, enhancing the specificity and effectiveness of cancer immunotherapy.

Development of chimeric antigen receptor (CAR) T-cell therapy targeting CD19 on B cells, demonstrating remarkable success against lymphomas.

The rapid commercialization and FDA approval of CAR T-cell therapy, highlighting the potential of translating scientific discoveries into lifesaving treatments.

The significance of checkpoint inhibitors, like anti-CTLA-4 and anti-PD-1, in unleashing the immune system to fight cancer more effectively.

The realization that a vast majority of cancers have unique mutations that can be targeted by the immune system, offering a path towards personalized cancer treatment.

Dr. Rosenberg's critique of the secrecy in medical research and advocacy for open sharing of knowledge to accelerate progress in cancer treatment.

The emotional toll of treating cancer patients and the challenge of balancing hope with the reality of treatment limitations.

The enduring impact of Dr. Rosenberg's mentorship, shaping the careers of numerous researchers and clinicians in the field of immunotherapy.

The vision for the future of cancer treatment, focusing on the utilization of the immune system to recognize and eliminate cancer through targeted therapies.

Transcripts

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