Aiming for a Cure With Immunotherapy

Our researchers are developing new cancer immunotherapies that could help patients achieve long-term remission.

Dr. Mike Jensen“Our goal isn’t to take therapies to market – it’s to give children a cure,” says Dr. Michael Jensen.

When our first cancer immunotherapy trial helped more than 90% of participants with relapsed or refractory acute lymphoblastic leukemia (ALL) achieve remission, many people wondered if we would push that therapy to market. Instead, we launched a full-court press to figure out why about half those patients relapsed within a year, and to find ways to help children beat cancer for good.

“Our initial results were an amazing step forward, but too many kids relapsed,” says Dr. Michael Jensen, who directs our Ben Towne Center for Childhood Cancer Research. “Our goal isn’t to take therapies to market – it’s to give children a cure.”

Making remission last

Dr. Colleen Annesley and childDr. Colleen Annesley is leading a clinical trial aimed at prolonging the persistence of the modified T cells.

This past year, we used what we learned from our initial trial to launch studies that could help solve the relapse problem and bring us closer to making CAR T-cell therapy more effective – and far less toxic – than bone marrow transplants.

In our initial trial – and in similar trials around the country – many patients relapsed because their CAR T cells either died off or became exhausted and stopped hunting cancer cells.

The CAR T cells were more likely to disappear quickly in patients whose bone marrow tests revealed low levels of CD19-positive cells before they started immunotherapy treatment. To address this, Dr. Colleen Annesley is leading a clinical trial of a “booster” approach that aims to prolong T-cell persistence. Patients can enter this trial if they’ve had CAR T-cell therapy and are at higher risk of seeing their CAR T cells lose persistence, or if there are signs the cells are losing steam.

Participants will receive infusions of cells that are modified to express CD19 instead of attacking it. Annesley hopes the added CD19 reinvigorates the CAR T cells so they keep attacking and bring patients closer to long-term remission.

“If this approach works, it could be built into future trials as a way to make sure that CAR T cells stay active long enough to get rid of more cancer cells,” she says.

Zeroing in on CD22

The therapy in our initial trial targeted the CD19 protein. But about 40% of participants relapsed when their cancer cells stopped expressing the CD19 protein.

“It became clear that we need a way to hunt down leukemia when it evades our therapies,” says Dr. Corinne Summers.

As a first step, we opened a clinical trial of a CAR T-cell therapy that targets CD22 – a potentially lifesaving option for patients who relapse with CD22-positive leukemia after CAR T-cell therapy.

“We’re hoping this will get those patients back into remission and give us some important insights on how CD22-positive cells respond to this therapy,” says Summers, the trial’s principal investigator.

Attacking two targets

Dr. Rebecca Gardner"We’re going to find ways to overcome every challenge, and we won’t give up until we have long-term cures," says Dr. Rebecca Gardner.

We’re also working to prevent this type of relapse altogether, with a new CAR T-cell that simultaneously targets CD19 and CD22.

“The idea is to go after both these proteins from the outset with a therapy that, hopefully, keeps attacking the leukemia when it evolves,” says Dr. Rebecca Gardner, who opened a trial of this therapy in November.

If this approach is effective, it could keep patients in remission and reduce relapse rates by as much as half.

“There’s so much excitement about immunotherapy’s potential that it’s easy to forget we have a lot to learn,” Gardner says. “But we’re going to methodically find ways to overcome every new challenge, and we won’t give up until we have long-term cures.”

We used what we learned from our initial trial to launch studies that could help solve the relapse problem.

Published in the Academic Annual Report, March 2017