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CAR Ts can move well beyond cancer, but will need to go allogeneic first

CAR Ts could move into autoimmunity, infections and more, if researchers can solve the allogeneic question.

Preclinical studies showing the utility of CAR T cells outside of cancer are ramping up, and developers have taken notice. But turning the modality into a general-purpose tool will require companies to break through safety and commercial barriers that still haven’t been sorted out in cancer.

The critical advance is for the technology to come off-the-shelf, and the risks of neurotoxicity and cytokine release syndrome to be mitigated.

“The system is incredibly versatile. The sky really is the limit,” said Poseida Therapeutics Inc. CEO Eric Ostertag. “You wouldn’t consider doing any of these non-oncology applications if you’ve got a product that costs several hundreds of thousands of dollars to make and it gives you grade 3 and 4 cytokine release syndrome and neurotoxicity that lands you in the ICU,” but the field is resolving those issues.

Poseida has allogeneic stem memory CAR T cells for a variety of non-oncology applications, which Ostertag says reflect that progress.

At least six CAR T cell companies have disclosed programs outside of cancer, one of which, Cabaletta Bio Inc., was founded in 2017 for the express purpose of taking the modality into new indications. The most advanced are about to enter Phase I testing (see Figure: “CAR T Programs Outside Oncology”).

Autoimmunity is seeing the most activity, followed by infections and transplant settings. All of these indications share a feature with cancer: an obvious cell type for the T cells to target. In autoimmunity, that is often the B cell; in infections, it’s the infected cell; and in transplants, it’s

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