025 Do CAR-T Cells Cause/Become Tumors?

For Whom the Cell Tolls: Cancer Biology and Other Stories

The basic answer is no. When faced with R-CHOP resistance, DLBCL patients now have the option to utilize genetically modified Chimeric Antigen Receptor T-cells (CAR-T) designed to hunt tumors. This episode investigates the recent controversy into if these super-cells can transition into a villainous tumor themselves. We cover a paper by Garcia et. al. that showcases how much power we are adding to CAR-T, even activating oncogenes to do it. Next, we transition to a large analysis from Stanford where 724 patients are examined, with 1 developing a T-cell tumor. Sequencing this case reveals that no synthetic vector DNA integrations or activity is within the tumor. It ends up revealing a great surprise about shared evolutionary pathways between B & T-cell progenitor stem cells. Enjoy the episode!

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Hamilton Paper (TCL After CAR-T): https://www.nejm.org/doi/full/10.1056/NEJMoa2401361

Garcia Paper (CARD11 in CAR-T): https://www.nature.com/articles/s41586-024-07018-7