A "living drug" that could change the way we treat cancer | Carl June

New Section

This section introduces the speaker's personal story and the topic of using the immune system to fight cancer.

The Potential of the Immune System

• Researchers have been studying the immune system as a way to fight cancer for over a century.

• Cancer vaccines have been disappointing, only working in virus-caused cancers like cervical or liver cancer.

• The immune system did not evolve to fight cancer but rather to fight pathogens from outside.

• The immune system has trouble recognizing cancer as a problem or attacks both cancer and normal cells, leading to autoimmune diseases.

Synthetic Immune Systems

• Synthetic immune systems are designed to recognize and kill cancer cells.

• Genetic engineering and synthetic biology are used to create these systems.

• B cells and T cells, natural components of the immune system, are used as building blocks.

• B cells produce antibodies that bind and kill bacteria, while T cells kill cells infected with viruses.

Chimeric Antigen Receptor T Cells (CAR T Cells)

• Genes for antibodies from B cells are inserted into T cells through genetic engineering.

• An HIV virus is used as a Trojan horse to bypass the T cell's immune system.

• The resulting CAR T cells act like supercharged killer T cells on steroids when they bind to tumor targets.

• CAR T cells stay alive in the body for years, making them the first living drug in medicine.

Challenges of Using CAR T Cells

• The only source of compatible T cells for patients is their own unless they have an identical twin.

• Patient-specific CAR T cells need to be grown in the laboratory before infusion.

Success with CAR T Cell Therapy

• In 2012, three patients with advanced chronic lymphocytic leukemia were treated with CAR T cells.

• One patient experienced a remarkable recovery after being comatose and given last rites.

• Two out of three patients achieved durable remissions, and one had a partial remission.

• CAR T cells successfully attacked and dissolved significant amounts of tumor in each patient.

New Section

This section highlights the groundbreaking potential of CAR T cell therapy in cancer treatment.

Living Drugs: The Paradigm Shift

• CAR T cells are considered the first living drug in medicine.

• Unlike traditional drugs that need to be taken repeatedly, CAR T cells stay alive and active for years.

• Infused CAR T cells can remain in the body for more than eight years, providing long-term surveillance against cancer.

A New Paradigm in Medicine

• The development of CAR T cell therapy marks the beginning of a new paradigm in medicine.

• It offers hope for previously incurable cancers and challenges traditional treatment approaches.

Personalized Treatment with Patient's Own Cells

• Growing patient-specific CAR T cells is crucial since compatible T cells must come from the patient themselves or an identical twin.

• Robust platforms have been developed to grow these personalized CAR T cells.

Evolution of CAR T Cell Therapy

• Initial testing of CAR T cells was done on patients with advanced HIV-AIDS, showing promising results but not a cure.

• Over the next decade, improvements were made to the design of CAR T cells before treating leukemia patients in 2010.

Remarkable Success Stories

• Three patients with advanced chronic lymphocytic leukemia received CAR T cell therapy in 2012.

• One patient experienced a miraculous recovery after being comatose and given last rites.

• Two out of three patients achieved durable remissions, and one had a partial remission.

• CAR T cells effectively attacked and dissolved significant amounts of tumor in each patient.

New Section

This section emphasizes the transformative impact of CAR T cell therapy on cancer treatment.

Unleashing Supercharged Killer T Cells

• When CAR T cells bind to their tumor targets, they act as supercharged killer T cells on steroids.

• They trigger a crash-defense buildup system in the body, rapidly multiplying by the millions to attack and kill tumors.

Long-lasting Effects

• Unlike traditional drugs that get metabolized and require repeated doses, CAR T cells stay alive and active for years.

• CAR T cells can remain in the body for more than eight years, providing ongoing surveillance against cancer.

Designer Cancer Treatment

• CAR T cells break the mold of traditional drugs by being personalized and long-lasting.

• They have a calculated half-life of more than 17 years, meaning one infusion can provide lifelong protection.

Overcoming Challenges

• The major challenge in using CAR T cell therapy is sourcing compatible T cells from the patient's own body or an identical twin.

• Robust platforms have been developed to grow patient-specific CAR T cells for effective treatment.

Transforming Medicine

• The development of CAR T cell therapy represents a new paradigm in medicine.

• It offers hope for previously incurable cancers and challenges conventional treatment approaches.

New Section

In this section, the speaker discusses the remarkable capabilities of CAR T cells in fighting cancer.

CAR T Cells: Punching Above Their Weight Class

• One CAR T cell can kill 1,000 tumor cells.

• The CAR T cell and its daughter progeny cells can divide and multiply until all tumor cells are eradicated. This is unprecedented in cancer medicine.

Successful Remission Cases

• The first two patients who received CAR T cell therapy achieved full remission and remain leukemia-free. They are considered cured.

• These patients had previously run out of treatment options and were considered modern-day Lazarus cases.

Forks in the Road

• The speaker expresses gratitude for the pivotal moments that led to breakthroughs in their research and treatment approach.

• Permission was obtained to treat children with acute leukemia, starting with a six-year-old patient named Emily Whitehead. She had relapsed multiple times despite previous treatments.

Emily's Case: A Critical Condition

• Emily was diagnosed with advanced, incurable leukemia that had spread to her bone marrow, liver, and spleen.

• After receiving CAR T cell therapy, Emily initially worsened and was admitted to the ICU in a comatose state on life support due to organ failure. Her fever reached as high as 106 degrees Fahrenheit for three days without an identifiable cause. Elevated levels of interleukin-6 (IL-6) were found in her blood at more than a thousandfold above normal levels.

A Fortuitous Connection

• The speaker's familiarity with experimental arthritis therapies led them to suggest using tocilizumab, an arthritis drug that blocks the effects of IL-6, to treat Emily's high fever and cytokine release syndrome (CRS).

• Despite initial skepticism, tocilizumab was administered to Emily, resulting in rapid improvement. After 23 days, she was declared cancer-free and remains in remission.

CRS and Immune System Response

• CRS, characterized by high fevers and coma-like symptoms following CAR T cell therapy, is now recognized as a positive sign of immune system activation against leukemia.

• Patients who do not experience CRS are often those who do not achieve remission. There is a strong link between CRS and the immune system's ability to eradicate cancer.

Impressive Results and FDA Approval

• CAR T cell therapy has shown a 90% complete remission rate in patients with advanced cancer, which is unprecedented in over 50 years of cancer research.

• The FDA approved CAR T cells for pediatric and young adult leukemia in August 2017, along with the use of tocilizumab to manage CRS side effects. This dual approval was a significant event in medical history.

Expansion into Lymphoma Treatment

• CAR T cell therapy has also been tested in adults with refractory lymphoma after its success in leukemia treatment.

The Advancement of CAR T-Cell Therapy

In this section, the speaker discusses the impressive results and durability of CAR T-cell therapy. They also highlight the FDA approval for advanced lymphoma treatment using CAR T cells and express excitement about the rapid advancements in this field. However, they also address concerns regarding the financial cost of CAR T-cell therapy.

Impressive Results and FDA Approval

• The results of CAR T-cell therapy have been equally impressive and durable to date.

• The FDA has approved the use of CAR T cells for treating advanced lymphoma six months ago.

Thrill and Concerns

• Many labs, physicians, and scientists worldwide have tested CAR T cells across various diseases, leading to rapid advancements in this field.

• Patients who were previously considered terminal have returned to healthy lives with CAR T-cell therapy.

• Long remissions observed with CAR T-cell therapy may potentially be a cure.

• The financial cost of CAR T-cell therapy is a concern, with costs up to $150,000 per patient for manufacturing the cells alone.

• Additional costs associated with treating complications like CRS can reach up to one million dollars per patient.

Cost vs Failure

• While there are concerns about the financial cost, it is important to consider that noncurative cancer therapies are also expensive, and patients still face mortality.

• Research should focus on making CAR T-cell therapy more efficient and affordable for all patients.

• As an evolving field, prices are expected to decrease as industry learns to do things more efficiently.

Persistence in Scientific Discoveries

• CAR T-cell therapy is the result of a 30-year journey filled with setbacks and surprises.

• Scientists require persistence, vision, and patience to overcome challenges in this field.

• The road to scientific discoveries like CAR T-cell therapy may not always be straightforward but can lead to significant advancements.