Jack (Jie) Huang, Vice President, Executive Director of American Botanical Drug Association, shared a post on LinkedIn:
“For years, CAR-T cell therapy has been one of the most effective weapons against blood cancers. It works by modifying a patient’s own T cells to recognize and kill diseased cells. But this success comes with a major limitation: each CAR-T product must be customized, which is time-consuming, expensive, and not always feasible. Wouldn’t it be great if CAR-T cells could be readily available to anyone, like an off-the-shelf drug? The biggest obstacle to achieving this vision is immune rejection—the patient’s immune system quickly recognizes donor T cells as foreign and eliminates them. The good news is that a new study now demonstrates a promising approach to overcome this problem.
Researchers developed a next-generation CAR-T product called SC291, designed to be “low-immunogenic.” These cells undergo multiple gene edits so that they not only carry a CD19 CAR targeting B cells but also lack their natural T cell receptor to prevent graft-versus-host disease. Furthermore, these cells have their HLA molecules removed to avoid immune recognition and overexpress CD47 (a “don’t eat me” signal), thereby suppressing immune attack. In early clinical trials involving patients with cancer and autoimmune diseases, researchers monitored the immune system’s response to these gene-edited cells. The results were remarkable. The fully low-immunogenic CAR-T cells did not trigger a new immune attack in any patient, regardless of dose or disease type.
Even more encouraging, patients who did not develop an antibody response to the CAR-T cells also experienced deep and sustained depletion of CD19-positive B cells, indicating that the therapy was effective not only in the blood but also in tissues. This suggests that immune evasion is not merely theoretical—it translates directly into better biological effects.
These findings provide strong early evidence that low-immunogenicity CAR-T cells can reliably circumvent allogeneic rejection, bringing the field closer to universal, off-the-shelf cell therapies. If validated in large-scale studies, this method could greatly expand the application of CAR-T therapy and open new doors for autoimmune diseases requiring immune reset. In short, by teaching CAR-T cells how to “camouflage” themselves, researchers may have opened a new chapter in cell therapy—powerful immunotherapy is no longer limited by the source of the cells.
Keywords: CAR-T therapy, low immunogenicity cells, off-the-shelf immunotherapy, immune evasion, CD19
Reference
Xiaomeng Hu et al, Cell Stem Cell 2025 (DOI: 10.1016/j.stem.2025.07.009).”