Drug Development

Investigators detail some of the hopes – and fears – behind Cellectis’ off-the-shelf CAR-T

Cellectis is right at the cutting edge of developing a new, off-the-shelf CAR-T that hopes to disrupt a market that has yet to be created. So far, about the only tangible human evidence of its potential durability has been seen in a pair of infants who were given Cellectis’ $CLLS lead therapy to ward off lethal cases of leukemia. And while an update on their condition shows that the two young patients are still alive and doing well months after treatment, one had to fight off graft-vs-host disease triggered by the therapeutic, a key sign of toxicity that investigators are watching closely.

Writing in Science Translational Medicine, the investigators handling these two cases offered details on their pioneering cases, using TALEN engineered cells to directly target B cell leukemia. Both children had relapsed, drug-resistant cases of B cell acute lymphoblastic leukemia.

In the first case, the investigators were allowed to use Cellectis’ off-the-shelf treatment on an 11-month-old child. Grade 2 skin GVHD developed but was successfully treated with steroids, and 18 months later the infant remains in remission.

Another baby girl was treated in much the same way after relapsing in late 2015 and responded well, without GVHD. An aggressive therapeutic intervention leaves her “clinically well at home.”

The survival times for these girls is not new. The data were first discussed at a scientific meeting in December, along with other cases involving shorter periods of post-treatment survival times. (Durability will be a key focus.) But this new report does provide more insights into the therapy, underscoring Cellectis’ rationale that the lead CAR-Ts now in late-stage development – which extract T cells from patients, engineer them and then infuse them back into patients – leave a lot to be desired. In some cases, the investigators note, patients aren’t going to have enough T cells left to reengineer into therapies, making an off-the-shelf alternative using cells from healthy donors essential.

The threat of GVHD, though, once again spotlights the severe adverse events that have been tied to these therapies. Juno’s $JUNO CAR-Ts have been tied to seven deaths from cerebral edema, including a tally of five for their lead program, which is now in limbo. Kite $KITE and Novartis $NVS, meanwhile, are racing to win the first approvals in the field.

Cellectis isn’t in the frank ranks of that race. But it’s angling to come in not far behind, if it can escape a catastrophe.


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