Myeloma treatment anito-cel shows potential for fewer side effects
Preclinical study compares treatment to approved cell therapies
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Anito-cel (anitocabtagene autoleucel), a cell therapy in clinical development as a potential treatment for myeloma, may be less likely to cause side effects than similar, approved myeloma cell therapies, according to a preclinical study.
Arcellx, which is developing anito-cel alongside Kite Pharma, said in a press release that it shared the findings at the 2026 Tandem Meetings, a multidisciplinary event focused on transplantation and cellular therapy, held Feb. 4-7 in Salt Lake City.
Anito-cel belongs to a class of cell therapies called CAR T-cells. T-cells are immune cells that can kill cancer cells. A CAR, short for chimeric antigen receptor, is a type of molecular weapon that directs T-cells to attack a target. The idea behind CAR T-cell therapies is to arm T-cells with a CAR that targets a cancer protein, enabling these immune cells to more effectively eliminate the cancer.
Anito-cel is an autologous therapy, meaning it uses T-cells that are taken from a patient and engineered in a lab before being infused back into the patient. The CAR in anito-cel is designed to target a protein called BCMA, which is often expressed by myeloma cells.
Other CAR T-cell therapies targeting BCMA, including Abecma (idecabtagene vicleucel) and Carvykti (ciltacabtagene autoleucel), are approved in the U.S. to treat certain myeloma patients. These therapies have demonstrated powerful anticancer activity, but are also associated with side effects including nausea, diarrhea, fatigue, and blood clots.
Tonic signaling
Side effects caused by CAR T-cell therapies may develop because the cells exhibit so-called tonic signaling: In other words, they are continuously in a low-level state of activity, secreting pro-inflammatory signaling molecules even in the absence of BCMA protein.
The researchers found that T-cells expressing the CARs used in Abecma and Carvykti exhibit tonic signaling, while the CAR used in anito-cel — which features a specific molecular motif called a D-domain — did not show evidence of this type of continuous inflammatory activity.
They also found that the CAR used in Carvykti recognizes not only BCMA but also Claudin-9 (CLDN9), an important protein involved in tissue structure. The CARs used in anito-cel and Abecma didn’t respond to this structural protein.
“Binding of CLDN9 in addition to BCMA could increase the risk of off-target toxicities,” Arcellx stated.
Anito-cel is in clinical testing for hard-to-treat myeloma. In a Phase 2 study called iMMagine-1 (NCT05396885), most patients were alive and free from disease progression two years after anito-cel treatment. A Phase 3 study called iMMagine-3 (NCT06413498) is testing the cell therapy in people with myeloma who have failed to respond or have relapsed after one to three prior lines of therapy. The Phase 3 trial is recruiting participants at sites in the U.S., Europe, Canada, Japan, and Australia.
