Year: 2024
Type: conference-abstract
Abstract: Chimeric antigen receptor (CAR)-T cells are a novel high-tech treatment modality that over the past years has gained an important role in the treatment of hematological malignancies. The basic principle for currently available CAR-T cells is that the patient’s own T lymphocytes are harvested and engineered in vitro to express a receptor on their surface of the desired specificity; in most cases a receptor that binds the CD19 molecule that is present on B-lineage cells. These cells are then reintroduced into the patient where they expand and bring about a very profound depletion of the target cells. Because autoreactive B-cells play an important role in many autoimmune diseases it has been proposed that CAR-T cells could be utilized to treat such diseases as well.Clinical experiences have now been published including small numbers of patients with a variety of autoimmune diseases including systemic lupus erythematosus (SLE), and for the most part these reports have been encouraging: along with the depletion of B cells, autoantibody titres decreased, and rapid and complete clinical responses were seen in many patients.1 2 B-cell reconstitution took place as expected, and vaccine responses were restored, but autoantibodies did not re-emerge, and clinical relapses did not occur in the lupus patients reported to date; in some patients a treatment-free remission for over two years has now been documented and CAR-T cell therapy was well-tolerated in these patients.The main questions that now must be addressed are:Is the abolition of autoreactive B-cell activity permanent?If so, is it sufficient for patients with SLE to remain free of disease?If so, can the necessary degree of B-cell depletion be achieved by other means?What are the true risks and possible side effects of CAR-T cell therapy in patients with autoimmune diseases?What role does ‘conditioning chemotherapy’ have in CAR-T cell therapy?How should patients be selected for CAR-T cell therapy?References Mackensen A, Müller F, Mougiakakos D, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022;28(10):2124–32. doi: 10.1038/s41591-022-02017-5.Muller F, Taubmann J, Bucci L, et al. CD19 CAR T-cell therapy in autoimmune disease - A case series with follow-up. N Engl J Med. 2024;390(8):687–700. doi: 10.1056/NEJMoa2308917.Learning Objectives At the end of this presentation participants will be able to:Discuss the published and reported experiences with CAR-T cells in the treatment of SLEExplain the basic principles of CAR-T cell therapy, the expected mechanistic effects in the patient, and the risks and potential side effects of the treatmentDiscuss the main outstanding questions currently before us regarding this therapyDiscuss the potential breakthroughs in the treatment of autoimmune diseases whilst recognizing that a disappointment is also possible
Source: Abstracts
Author: Ronald van Vollenhoven
Institution: Amsterdam University Medical Centers
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4402272537