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CAR T Cells and IL-9 Signaling in Solid Tumors

1:14:43 recording · AUTO · 4 speakers

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Brief overview

Two papers: IL-9 supercharges CAR T cells in solid tumors, and tattoo ink reshapes vaccine responses.

  1. IL-9 receptor keeps CAR T cells out of exhaustionCAR T cells given the native IL-9 receptor expanded more, infiltrated tumors, kept CAR expression and trended toward early memory instead of exhaustion.
  2. Local cytokine delivery limits on-target off-tumor damageInjecting IL-9 by adenovirus into the tumor means the CAR T cells are super-activated at the tumor site and not elsewhere.
  3. Tattoo ink reaches lymph nodes and alters vaccine responsesInk accumulates in draining lymph nodes for months, kills macrophages, and moved antibody responses down for mRNA vaccine and up for inactivated flu vaccine.
Executive Summary AI
  • Cindy Leifer opens Immune 101 with a brand-new Immunity paper from Carl June's lab, first author Sophia Castelli, testing whether adding the native IL-9 receptor to CAR T cells makes them work in solid tumors, which are over 90% of cancers.4:56
  • In a pancreatic ductal adenocarcinoma mouse model, delivering IL-9 locally by adenovirus to tumors treated with IL-9-receptor CAR T cells produced complete remission in 5 out of 10 mice, while CAR T alone, receptor without cytokine, or cytokine alone did nothing.15:22
  • In a human PDAC xenograft, 10 out of 10 mice went into remission and stayed resistant on re-challenge, because the IL-9 signal pushed the cells toward early memory rather than exhaustion and lowered PD-1 and TIM-3.16:52
  • Vincent Racaniello then covers a PNAS paper, first authors Arianna Capuchetti and Giuliana Falivene, showing tattoo ink travels from the foot pad to the popliteal lymph node within 24 hours, is taken up mainly by medullary macrophages, and kills them by necrosis and apoptosis.27:32
  • Tattooing two days or two months before vaccination lowered anti-spike antibody to the Pfizer mRNA vaccine, but the same inks increased IgM and IgG to an inactivated influenza vaccine, an opposite effect the hosts call the paper's most striking result.56:50
Key Quote
“greater than 90% of tumors are actually solid tumors.”
— Cindy Leifer9:38
Key Quote
“they got a complete remission out of 5 out of 10 of the mice.”
— Cindy Leifer15:22
Key Quote
“However, I always wanted a little virus tattoo on my hand.”
— Vincent Racaniello29:39