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Journal Club: Slaying the Sleeper Cells of Aging with CAR T | a16z

Key Takeaways

  • CAR T is a revolutionary therapy which uses engineered T cells to identify and destroy specific cells
  • A recent study demonstrated promise in using CAR T cells to recognize and kill senescent cells
  • CAR T therapy has the potential to restore health, not just combat cancer

Introduction

Jorge Conde (@jorgecondebio), Andy Tran (@andy23tran), and Lauren Richardson (@lr_bio) discuss new research using engineered T cells to attack and destroy harmful senescence that occurs with aging.

What is CAR T Therapy?

  • CAR T stands for chimeric antigen receptor T cells
  • CAR T is a revolutionary therapy which uses engineered T cells to identify and destroy specific cells
  • CAR T therapy is promising but has also been shown to lack potency and precision
  • Without specificity, CAR T therapy will kill healthy cells as well as unhealthy ones
  • CAR T therapy is primarily used in cancer treatment, leukemias, and lymphomas 

The Two Sides of Senescence

  • Senescence is a biological process where cells stop dividing and go to sleep
  • Senescence has a critically protective function because it stops potentially disease-causing cells
  • On the flip side, if too many cells become senescent it can lead to inflammation and disease
  • In metabolically healthy conditions, harmful senescent cells do get cleared out by the immune system
  • As immune response weakens with age, senescent cells build up and trigger issues   

Questions to Consider When Evaluating CAR T Therapy for Senescent cells

  • Can we identify biomarkers for senescent cells to properly program CAR T cells with specificity?
  • Can CAR T cells be used to clear senescent cells?
  • Does the removal of senescent cells have a clinical impact?

Using CAR T Therapy for Senescent Cells

  • Recent advances show promise for the use of CAR T as a possible for aging treatments
  • New specificity has been developed in CAR T to enable the cells to recognize more than just cancer
  • In a new study, researchers used CAR T cells to recognize and kill senescent cells
  • Researchers validated their model with cancer then programmed CAR T cells to attack liver fibrosis, atherosclerosis, and diabetes in mice

Future Implications  

  • Senescence is a key hallmark of aging
  • We are seeing a paradigm shift in our use of CAR T therapy: instead of using CAR T therapy to kill cells which shouldn’t be there (i.e., cancer) – we can use CAR T therapy to reengineer aging immune system
  • CAR T therapy has the potential for restoring health, not just combating cancer
  • With additional research, CAR T therapy could be the standard for treating a wide range of diseases

Limitations of CAR T therapy

  • It would take too long to have clinical studies in aging in humans
  • High cost
  • Difficult scaling: Do T cells need to be specific to the person or can there be a universal donor to increase the ability to scalability?
  • There were some negative side effects related to dosing, which have to be resolved before widespread clinical use
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