Shooting for immune

The theory that T cells could be taken from a cancer patient and genetically engineered to become cancer killers was ambitious-bordering-on-crazy when it was first proposed. According to CAR-T cell therapy pioneer Carl June, “No one ever really thought it would work.”

Less than 40 years later, the U.S has seven FDA-approved CAR-T cell therapies and has treated 30,000 blood cancer patients. Efforts to move the therapies into other types of cancer, such as solid tumors, have been ongoing. But lately, the use of CAR-T cell therapies in autoimmune diseases has been stealing the show.

The potential for the therapies to tackle unmet needs in autoimmune disease treatment has been on the lips of the industry since the dataset from a German research study in 2022 demonstrated that treatment with a CD19 CAR-T cell therapy could induce drug-free remission in lupus patients. The group wasn’t the first to propose the idea that CAR-T cell therapies could eliminate the antibody-producing B cells that have malfunctioned in many autoimmune diseases, but their data sent the space soaring. 

Enthusiasm has been ignited by a surge of new entrants, fresh investments, and clinical momentum. There are now close to 30 CGT companies pursuing development in autoimmune diseases, and over 100 global clinical trials.

Immunology and inflammation is a buzz-worthy sector even without CAR-T developers in the airspace. Recently the industry has seen billion-dollar deals from the likes of Sanofi, Vertex, Biogen, Eli Lilly — all chasing more durable treatments for the subsets of patients that fail several lines of therapies, continue to relapse, or develop more progressive diseases. Despite advancements, fewer than 10% of people with an autoimmune disease can reach durable remission. And there are still no cures.

For the CGT sector, making an impact in autoimmune disease will require more than just clinical promise. It will demand that developers confront the field’s limitations head-on. The costly scale-up and manufacturing issues that have become the hallmark of the field simply will not fly in a space dominated by well-established lower-cost standards of care. Commercial viability – pricing that facilitates both access and profit — will be crucial.

As you will read in this issue’s cover story, developers are not shying away from the challenge. Companies with commercialized autologous CAR-T cell therapies, such as BMS and Novartis, are rolling out new manufacturing platforms that facilitate faster turnaround times, increased yield, higher purity and lower costs.

Fresh efforts are being made to improve scalability, with several biotechs developing therapies on allogeneic platforms. In the realm of these off-the-shelf treatments, new CAR constructs could facilitate better clearance of B cells in organ tissues. New cell sources, such as iPSC lines, could offer almost unlimited scalability along with more favorable safety profiles. Companies are also taking on durability challenges with CAR constructs that target multiple antigens simultaneously, aiming to prevent antigen escape, a common cause of tumor relapse when CAR-T cell therapies are used in cancer.

Breakthrough treatments in an area of unmet need inevitably draw attention. While it is still early days for CGTs in autoimmune disease, the field is actively pushing its own limits, working to translate scientific excitement into better, more accessible products. Not only could this lift cell therapies to new heights, but it could redefine them entirely.