Ep. 94: “Engineering Immunity” Featuring Dr. Lili Yang
Dec 3, 2024
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Dr. Lili Yang, a renowned professor at UCLA specializing in immunotherapy for cancer, dives into her innovative research on engineering off-the-shelf treatments. She discusses the exciting potential of CAR-NKT cells derived from stem cells, highlighting advancements in accessibility to therapies. Lili also explores the surprising link between serotonin, SSRIs, and their impact on cancer treatment efficacy. Her insights challenge traditional views, merging the realms of mental health and immunology in groundbreaking ways.
The development of off-the-shelf immunotherapies could revolutionize cancer treatment by making therapies more accessible and less expensive for patients.
Recent findings highlight the significant role of mitochondria in determining cell death pathways, suggesting inflammation may shift cell fate in immune responses.
Exploring serotonin’s influence on T cell functionality could lead to enhanced cancer therapies, especially for patients resistant to traditional treatments.
Deep dives
Developing Off-the-Shelf Immunotherapies
The podcast discusses the innovative approach of creating off-the-shelf immune cell therapies to improve accessibility and reduce costs for patients needing cancer treatments. By engineering immune cells, researchers aim to develop therapies that do not require personalized customization for each patient, which is currently time-consuming and expensive. The focus is on using hematopoietic stem cells from cord blood, which can be expanded and modified to create a large number of therapeutic cells. This method seeks to address logistical challenges in therapy delivery while providing effective treatments to a broader population.
The Role of Mitochondria in Immunity
A recent study highlighted in the episode explores the critical role of mitochondria in regulating cell death mechanisms, particularly apoptosis and pyroptosis. Mitochondrial ATP production is shown to influence these processes, with decreased ATP levels favoring the activation of the NLRP3 inflammasome, leading to pyroptosis instead of apoptosis. This finding suggests that inflammation could be a driving factor in determining cell fate during immune responses. Understanding this relationship enhances knowledge of how inflammatory signals can inhibit apoptosis, which has implications for various diseases, including cancer.
Investigating Long COVID and Spike Protein Persistence
The podcast highlights a controversial study investigating the potential long-term effects of COVID-19, particularly relating to the persistence of the spike protein in the central nervous system. The study suggests that the spike protein may contribute to neurological symptoms reported in long COVID patients, even in those who never experienced severe illness. Using advanced imaging techniques, researchers found spike protein remnants in postmortem brain tissues, raising questions about the role of viral proteins in ongoing neurological issues. This research could deepen the understanding of long COVID and inform future treatment strategies.
Checkpoints Beyond PD-1 and CTLA-4
The discussion includes a focus on expanding the scope of immune checkpoint therapy beyond the well-known targets PD-1 and CTLA-4. Researchers are examining molecules that interface between the immune and nervous systems, particularly how serotonin regulation can influence T cell functionality. This approach has revealed that antidepressant drugs, designed to target serotonin pathways, may enhance anti-tumor immune responses. By exploring these alternative pathways, the potential exists to improve treatment options for patients who do not respond to traditional therapies.
B1 Cells and Viral Defense Mechanisms
A study discussed in the podcast investigates the role of a unique subset of B cells, known as B1 cells, in defending against reactivation of endogenous retroviruses. These innate-like B1 cells appear capable of recognizing viral glycoproteins, offering a protective mechanism against potential reactivation from their genomic remnants. Research suggests that this pre-existing antibody repertoire can provide a significant advantage in controlling viral pathways. Understanding this protective function could lead to new therapeutic strategies for managing viral infections and enhancing immune surveillance.
Dr. Lili Yang is a Professor of Microbiology, Immunology, and Molecular Genetics at the University of California, Los Angeles. Her research centers on deciphering the molecular mechanisms regulating anti-cancer immune responses, exploiting knowledge to develop novel immunotherapies for treating cancer, and translating these new cancer immunotherapies from bench to bedside. She talks about engineering off-the-shelf immunotherapies to fight cancer and generating CAR-NKT cells from hematopoietic stem and progenitor cells. She also discusses the role of serotonin and how SSRIs can affect cancer therapy efficacy.
Endogenous Retrovirus Antibodies – An antibody produced by endogenous retrovirus-reactive B cells recognized glycans of a broad range of enveloped viruses.
opens December 10!
