Harnessing immune calls to fight cancer - A success story | Bhuvana Ramaswamy | TEDxInnovationDr
This presentation by a breast medical oncologist argues that immunotherapy manipulates immune cells to fight cancer, an epic story spanning 150 years, and concludes by calling for global connection among stakeholders to achieve a cancer-free world. The central mechanism involves unleashing the immune system's natural defenses, specifically targeting negative regulators with checkpoint inhibitors, while balancing risks like autoimmunity and establishing collaboration with diverse stakeholders.
## Speakers & Context
- Breast medical oncologist and cancer researcher.
- Personal link to the topic: Lives with cancer due to immunotherapy treatment.
- Time constraint: Must convey a 150-year epic story in 15 minutes.
## Theses & Positions
- Immunotherapy is a major breakthrough saving lives by manipulating the immune system to fight cancer.
- Cancer development occurs when carcinogens cause DNA damage, and cancer cells successfully confuse or evade the immune system's natural "proofreading" mechanisms.
- The principle of immune therapy is making cancer cells more visible or improving immunity so that immune cells can destroy them.
- The ultimate goal is to create a cancer-free world by connecting all necessary stakeholders.
## Concepts & Definitions
- **Carcinogen:** A substance that causes cancer, encountered via breath, ingestion, touch, or taste.
- **DNA:** Genetic code that instructs normal cells on how to function.
- **Cancer:** Occurs when DNA breaks are misinterpreted, leading to rogue cells that multiply uncontrollably instead of dying through the normal cell cycle.
- **Immune Surveillance:** The continuous function of immune cells to watch out for and eliminate damaged cells.
- **Immune Editing:** The action of immune cells removing bad cells.
- **Immune Escape:** The process where cancer cells confuse the immune system and camouflage themselves.
- **Negative Regulators of Immune Cells:** Molecules (like PD-L1/CTLA-4) that suppress the immune response, which cancer cells exploit to protect themselves.
- **Checkpoint Inhibitors:** Drugs that function by inhibiting negative regulators, allowing T cells to resume attacking cancer cells.
- **Autoimmune Side Effects:** Immune cells, while fighting cancer, can mistakenly attack the body's own cells (e.g., thyroid or pituitary).
## Mechanisms & Processes
- **Carcinogen Action:** Carcinogens $\rightarrow$ DNA damage $\rightarrow$ DNA breaks $\rightarrow$ Misinterpreted material $\rightarrow$ Rogue cell proliferation $\rightarrow$ Tumor/Cancer.
- **Immune System Defense:** Immune cells act as "proofreaders" $\rightarrow$ DNA repair system attempts correction $\rightarrow$ Failure leads to potential cancer.
- **Cancer Evasion:** Cancer cells become "very smart" $\rightarrow$ They confuse immune cells and "camouflage themselves."
- **Immune Therapy Principle:** 1) Make bad cells more visible OR 2) Improve immunity $\rightarrow$ Immune cells neutralize the cancer.
- **Checkpoint Inhibitor Action:** Cancer cells use negative regulators $\rightarrow$ Inhibitors block these negative regulators $\rightarrow$ T cells can attack the cancer.
## Timeline & Sequence
- **Pre-modern History:** Concepts traceable to the late 1800s and early 1900s.
- **Early Immunology:** Dr. Bill Coley demonstrated the concept by injecting infected material from other patients into patients with bone cancer, showing reduction.
- **Scientific Progress:** International collaborations have led to discoveries culminating in modern immunotherapy.
- **Mortality Reduction:** From 1991 to 2017, cancer-related mortality was reduced by **1.1%**; between 2016 to 2017, it dropped by **2.2%**.
- **Meta-analysis:** Comparing the initial phase (before immunotherapy) to the present shows a massive shift in outcomes for metastatic melanoma (one-year survival rate increased from **42% to 55%** between 2013 and 2017).
## Named Entities
- Dr. Bill Coley: Considered the father of immunology.
- Pelotonia Institute of Oncology: Facility where novel breakthroughs are being attempted.
- NCI (National Cancer Institute): Agency that needs support for research.
## Numbers & Data
- Annual incidence of new cancers worldwide: **17 million**.
- Global population: **7.8 billion**.
- Chemotherapy comparison: Immunotherapy is *not* chemo.
- Mortality reduction (1991–2017): **1.1%**.
- Mortality reduction (2016–2017): **2.2%**.
- Metastatic melanoma 1-year survival rate (2013): **42%**.
- Metastatic melanoma 1-year survival rate (2017): **55%**.
- Number of cancers addressed by immunotherapy (currently): **14**.
- Number of drugs approved for these cancers: **7**.
## Examples & Cases
- **Analogy for Immune Cells:** Viewing immune cells as "somebody who proofreads," comparing DNA sequence to jumbled words.
- **The Trojan Horse Analogy:** Describing cancer evasion as a terrorist getting through a TSA checkpoint.
- **Treatment Modality Examples:**
- **Vaccines:** Passively giving immunity to patients.
- **Cytokines:** Injecting immune "juices" to kill cancer cells.
- **Adoptive Cell Therapy:** Taking patient T cells, modifying them in the lab, and returning them.
- **Oncolytic Viruses:** Giving an attenuated virus into a tumor, where it multiplies, forcing the immune system to kill the virus and subsequently the tumor.
- **Bladder and Kidney Cancer Example:** Demonstrated using green lines on a graph to show that patients responding to checkpoint inhibitors experienced tumor reduction that *remained* low for a long duration.
- **Successful Cancers:** Melanoma, lung cancer, liver cancer, kidney cancer, breast cancer, and others.
## Tools, Tech & Products
- **Checkpoint Inhibitors (Molecules):** PD-L1, CTLA-4.
- **Immune Cell Sources:** T cells (from the patient).
- **Treatment Types:** Vaccines, Cytokines, Adoptive Cell Therapy, Checkpoint Inhibitors, Oncolytic Viruses.
## Trade-offs & Alternatives
- **Immunotherapy vs. Chemo:** Immunotherapy is not chemotherapy.
- **Immune Modulation Balance:** The immune response must be "commissioned to the injury"—strong enough to fight cancer, but not so strong as to cause severe autoimmunity (e.g., affecting the thyroid or pituitary).
- **Holistic Approach:** The need to combine basic science, oncology, endocrinology, and rheumatology.
## Counterarguments & Caveats
- **Immune Resistance:** Not all tumors respond; some continue to grow (need for further research).
- **Toxicity:** Immune activation can trigger autoimmune side effects.
- **Scope Limitation:** The presentation only covers **14** specific cancers, leaving many others untreated.
## Conclusions & Recommendations
- The future of cancer care requires a "holistic approach" that connects multiple scientific disciplines.
- Stakeholder connection is critical: connecting donors, community members, patients (willing to participate in trials), funding agencies, and pharmaceutical companies.
- The ultimate goal is to "create a cancer free world."
## Implications & Consequences
- Immunotherapy has the potential to transform cancer into a chronic disease manageable over long periods.
- The successful manipulation of the immune system represents a fundamental shift in oncology.
- The impact is measurable in decreased mortality and improved survival rates for aggressive cancers like metastatic melanoma.
## Verbatim Moments
- *"an epic story that spans over 150 years."*
- *"If we connect well we can create a cancer free world and that is our goal today and every day and we will get there"*
- *"My life has been a privilege to be able to take care of patients and do research but i am also gifted i'm it's a gift every day because it is this immunotherapy that's keeping me alive"*
- *"we don't want to take an ak-47 for a simple family squabble."*
- *"we need to connect with all the funding agencies we need to connect with the pharma who have to make the drug we need to connect with government officials"*
- *"this isn't a short story"*