AbbVie is teaming up with the California Institute for Biomedical Research (Calibr), a division of Scripps Research Institute, to design and develop a new generation of switchable chimeric antigen receptor T-cell (CAR-T) therapies for cancer. The partnership shows AbbVie’s excitement about new, controllable versions of cell therapy that are just now beginning to move into clinical studies.
Investments in cell therapies have gained steam since the first two CAR-T medicines were approved by the U.S. Food & Drug Administration last fall. Sold by Novartis and Gilead Sciences, they attack cancer with a patient’s own T cells.
Making the CAR-T therapies requires removing T cells from a person’s body, engineering them to produce a synthetic protein called a chimeric antigen receptor, and reinfusing them into the patient’s blood. The CAR then detects a particular antigen on cancer cells and destroys them.
Currently, scientists must engineer a new CAR protein for every new cancer antigen that scientists want to target. Researchers at Calibr, led by Director of Protein Sciences Travis Young, have devised a new system that could use the same CAR T-cell therapy to target many different tumors. The trick is adding adapter molecules, also known as antibody switches, which are proteins that bind the same CAR at one end but bind different cancer antigens at the opposite end.
“Here the cells are the hardware and the switches are the software,” Young explains. “We can use the switches to program the cells to go wherever they are needed.”
The approach could allow Calibr to quickly develop CAR-T therapies targeting many types of cancers, including solid tumors, which have been much tougher to eradicate with CAR-Ts than blood cancers.
In the partnership with AbbVie, Calibr will receive an up-front payment and will grant AbbVie exclusive access to its switchable CAR-T system for up to four years. AbbVie may acquire an exclusive license for the system during that time. Calibr will also develop multiple switchable CAR-Ts directed at several solid-tumor antigens picked by AbbVie. The duo isn’t disclosing financial details about the partnership, but Calibr Chief Operating Officer Matt Tremblay says, “This is the biggest deal that we’ve done by far.”
Both approved CAR-T therapies, Kymriah and Yescarta, target an antigen called CD19, found on B cells in rare blood cancers. The therapy sometimes wipes out the B cells, and thus cancer. But if the cancer cells mutate and stop producing CD19, CAR T cells can no longer spot them, and the cancer can relapse.
Calibr’s switchable CAR-Ts could offer a way around this problem. If a person’s cancer relapses after the CD19 switch is administered, doctors could transition to using a switch for another cancer antigen, such as CD20 or CD22, without having to make or infuse new CAR T cells.
Calibr plans to launch a clinical trial testing the CD19-directed antibody switch in people with lymphoma next year. If successful, future trials could add switches targeting additional antigens. AbbVie has the option to acquire this program as well.