The Same Technology Used in Cancer Immunotherapy Could Help Target Alzheimer’s

Inspired by advances in cancer therapy, a team at the Buck Institute has engineered immune cells equipped with specialized targeting devices called chimeric antigen receptors (CARs) that can distinguish and respond to tau tangles and various forms of toxic amyloid plaques, both of which are implicated in Alzheimer’s disease pathology. The proof-of-concept study, now online at the Journal of Translational Medicine, holds the promise of being able to precisely deliver therapeutic drugs directly to affected areas of the  brain with fewer side effects.

“Protein tangles and plaques have been the focus of Alzheimer’s treatments for decades,” says Walton. “What we’re showing for the first time is that immune cells can be trained to recognize not just amyloid or tau in general—but specific forms of these proteins that are thought to be most toxic. It’s a bit like an autonomous taxi – you type in the destination address and the engineered receptor cells end up exactly where you want them to be.”

While based on the same methods used to create targeted therapies for cancer, Walton points out a significant difference in this work. “It’s important to note that this technology does not involve the same toxicity seen in CAR-T cells,” he explains Those receptor cells are designed to kill cancer cells. Our cells will be designed to heal. We want to save neurons.”

Walton was thrilled with how well the technology worked. He says the team did not expect to simply get the antibody sequences and put them in the receptors on the cells and see most of them work. Four out of five receptors did.

The work follows the same research path that was used to develop CAR-T therapeutics for cancer. The initial work was done in mouse immune cells, which was the case in this study. The next step involves engineering and validating the process in immune cells that include a therapeutic “payload.” If successful, those engineered cells would be put into an Alzheimer's mouse model.

Walton says the technology goes beyond Alzheimer’s; it could be applicable to any disease that involves the immune system and extracellular aggregates. For that reason, the team decided to be fully transparent when publishing their results. “A lot of researchers will test their constructs and report out results, but they won't give you the complete amino acid sequences to make them. You really have to dig through the scientific literature and patents to figure them out, and even then, some just aren’t available,” he says. “But the sequences are in our study. They're there and anyone could use them for their cells, whatever cell type they are, which is the way research should be.”

“In addition to furthering our own research, we see this transparency as a gift to the community,” says Andersen. “Furthering research for everybody is what this team is all about.”

Reference: Siebrand CJ, Bergo NJ, Lee S, Andersen JK, Walton CC. Chimeric antigen receptors discriminate between tau and distinct amyloid-beta species. J Transl Med. 2025;23(1):605. doi: 10.1186/s12967-025-06572-6

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