Metabolic changes in T cells may limit CAR potential in kids

“Normal, healthy donor T cells cluster together in terms of metabolic pathways that are active or inactive,” Dr Barrett explained.

“[P]atients who had leukemia and the Wilms’ tumor patients could make successful CAR T cells from those samples. On the other hand, solid tumors and a Hodgkin disease patient look like they have a very different metabolic profile. And that is associated with failure to make a good CAR T cell.”

The investigators were able to get the T cells to shift metabolic pathways by “essentially force-feeding T cells things like fatty acids so they don’t use as much glucose,” Dr Barrett said.

“We’ve had some success in force-feeding them essentially neutral amino acids and others like arginine. And so you can actually potentially provide a T cell with an attractive alternative fuel source.”

Dr Barrett noted that the findings have already altered practice for children at his institution.

They now collect T cells early even if the patient is not eligible for a CAR trial, “simply because we know that cumulative chemotherapy is going to progressively deteriorate the likelihood that those cells will make a functional CAR product, and we’ve been recommending that to other centers,” Dr Barrett said.

“We’re trying to understand what goes into making the best starting material so that we can alter our approaches to make sure that we make a highly functional CAR T-cell product not only for kids with leukemia and CART19, but also potentially for solid tumor CARs as we try to develop those in the future.”