Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction

Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate senescent cells ('senolytics') partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting the senescence-associated protein urokinase plasminogen activator receptor (uPAR), and we previously showed these can safely eliminate senescent cells in young animals. We now show that uPAR-positive senescent cells…

• CR
  Cancer Research Institute

  Award: P30 CA008748
• MS
  Memorial Sloan-Kettering Cancer Center

  Award: CA008748
• “C
  “la Caixa” Foundation
• CS
  Cold Spring Harbor Laboratory

  Awards: P30CA045508, 5P30CA045508, U01CA224013, U01CA210240
• NH
  Northwell Health
• S
  Servier
• NI
  National Institutes of Health

  Awards: P30 CA008748, 1DP5OD033055-01, R01CA229699, U01CA224013, S10OD028632-01, 1R01CA190092, U01AG077925, 5P30CA045508, S10OD028632, U01CA210240, R01 grant, 1R01CA188134, 5P30CA45508
• CF
  Common Fund