Bulliard Yannick, Freeborn Robert, Uyeda Molly Javier, Humes Daryl, Bjordahl Ryan, de Vries David, Roncarolo Maria Grazia
Department of Research and Development, Tr1X, Inc., San Diego, CA, United States.
Division of Hematology, Oncology, Stem Cell Transplantation, and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States.
Front Immunol. 2024 Dec 4;15:1509956. doi: 10.3389/fimmu.2024.1509956. eCollection 2024.
Autoimmune diseases, characterized by the immune system's attack on the body's own tissues, affect millions of people worldwide. Current treatments, which primarily rely on broad immunosuppression and symptom management, are often associated with significant adverse effects and necessitate lifelong therapy. This review explores the next generation of therapies for immune-mediated diseases, including chimeric antigen receptor (CAR) T cell and regulatory T cell (Treg)-based approaches, which offer the prospect of targeted, durable disease remission. Notably, we highlight the emergence of CD19-targeted CAR T cell therapies, and their ability to drive sustained remission in B cell-mediated autoimmune diseases, suggesting a possible paradigm shift. Further, we discuss the therapeutic potential of Type 1 and FOXP3 Treg and CAR-Treg cells, which aim to achieve localized immune modulation by targeting their activity to specific tissues or cell types, thereby minimizing the risk of generalized immunosuppression. By examining the latest advances in this rapidly evolving field, we underscore the potential of these innovative cell therapies to address the unmet need for long-term remission and potential tolerance induction in individuals with autoimmune and immune-mediated diseases.
自身免疫性疾病的特点是免疫系统攻击身体自身组织,全球数以百万计的人受其影响。目前的治疗方法主要依赖广泛的免疫抑制和症状管理,常常伴有显著的副作用,且需要终身治疗。本综述探讨了免疫介导疾病的下一代疗法,包括嵌合抗原受体(CAR)T细胞疗法和基于调节性T细胞(Treg)的方法,这些疗法有望实现靶向性的、持久的疾病缓解。值得注意的是,我们强调了靶向CD19的CAR T细胞疗法的出现,以及它们在B细胞介导的自身免疫性疾病中推动持续缓解的能力,这表明可能会出现一种范式转变。此外,我们还讨论了1型和FOXP3 Treg以及CAR-Treg细胞的治疗潜力,它们旨在通过将活性靶向特定组织或细胞类型来实现局部免疫调节,从而将全身免疫抑制的风险降至最低。通过审视这一快速发展领域的最新进展,我们强调了这些创新细胞疗法在满足自身免疫性和免疫介导疾病患者对长期缓解和潜在耐受诱导的未满足需求方面的潜力。