After scrapping plans to grab a quick FDA nod for Rova-T, AbbVie is licensing CAR-T technology from Calibr to create safer, “switchable” CAR-T treatments for solid tumors.
AbbVie will pay an undisclosed license fee in return for exclusive access to Calibr’s platform for up to four years. While its primary focus is solid tumors—historically difficult to treat with CAR-T—the Big Pharma has the option to identify other targets, including blood cancers, and to license Calibr’s cell therapy programs that are already under way. This includes Calibr’s lead program, which is set to enter the clinic for lymphoma next year.
The pair will share responsibility for preclinical development, and AbbVie will take on clinical development and commercialization. Calibr will stand to reap success-based milestone payments and royalties.
Aside from challenges in solid tumors, researchers and companies working on CAR-T have run into issues with safety, specificity and patient relapse. The treatment essentially involves taking a patient’s T cells, modifying them to better recognize and attack a certain cancer, and putting them back into the patient, after which their activity can’t be controlled.
Calibr’s CAR-T platform is antigen agnostic and is “absolutely dependent” on antibody-based switches, said Travis Young, director of protein sciences at Calibr.
Calibr hopes its tech will lead to a universal CAR-T system, in which T cells would be modified the same way for each patient, regardless of tumor type, rather than developing a new CAR-T for each indication. The type of antibody switch used would determine the target, “switch on” the treatment and control its strength, Young said.
In addition to controlling CAR-T activity, the switches could also combat patient relapse, which happens when a patient’s cancer “hides” from the CAR-T cells by “losing” the antigen the cells are engineered to find. In this case, Young said, a different switch targeting a different antigen could be deployed.
“We’ve been working on this for a long time. We’re excited to see ‘switchable’ CAR-Ts getting a lot of attention now,” said Calibr COO Matt Tremblay. “AbbVie has a fresh perspective, it’s not in the cell therapy space in any significant way now that’s well known. […] It’s the right time to team up with somebody who is bold enough to go for a collaboration of the scope you see outlined [here].”
Many players are working on what is being called CAR-T 2.0, the next generation of CAR-T treatments designed to be safer and less complicated and time-consuming to produce. Researchers from Boston University are working on a split, programmable, universal system that aims to solve the same problems Calibr is trying to address. And researchers at Cellectis are incorporating a safety switch into CAR-T constructs themselves to eliminate the risk of imbalanced populations of safeguard molecules and CAR-T cells.