CD19 CAR-T cell therapy: a new dawn for autoimmune rheumatic diseases?

Carlos Rangel-Peláez; Laura Martínez-Gutiérrez; María Tristán-Manzano; José Luis Callejas; Norberto Ortego-Centeno; Francisco Martín; Javier Martín

doi:10.3389/fimmu.2024.1502712

CD19 CAR-T cell therapy: a new dawn for autoimmune rheumatic diseases?

Front Immunol. 2024 Dec 17:15:1502712. doi: 10.3389/fimmu.2024.1502712. eCollection 2024.

Authors

Affiliations

¹ Institute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
² LentiStem Biotech, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
³ Systemic Autoimmune Disease Unit, Hospital Clínico San Cecilio, Instituto de Investigación Biosanitaria Ibs, Granada, Spain.
⁴ Department of Medicine, University of Granada, Granada, Spain.
⁵ Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, Instituto Biosanitario de Granada (ibs.GRANADA), University of Granada, Granada, Spain.
⁶ Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
⁷ Instituto Biosanitario de Granada (ibs.GRANADA), University of Granada, Granada, Spain.

^# Contributed equally.

Abstract

Autoimmune rheumatic diseases (ARDs), such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, involve dysregulated immune responses causing chronic inflammation and tissue damage. Despite advancements in clinical management, many patients do not respond to current treatments, which often show limited efficacy due to the persistence of autoreactive B cells. Chimeric antigen receptor (CAR)-T cell therapy, which has shown success in oncology for B cell malignancies, targets specific antigens and involves the adoptive transfer of genetically engineered T cells. CD19 CAR-T cells, in particular, have shown promise in depleting circulating B cells and achieving clinical remission. This review discusses the potential of CD19 CAR-T cells in ARDs, highlighting clinical achievements and addressing key considerations such as optimal target cell populations, CAR construct design, acceptable toxicities, and the potential for lasting immune reset, crucial for the safe and effective adoption of CAR-T cell therapy in autoimmune treatments.

Keywords: CD19 CAR-T; autoimmune rheumatic diseases; rheumatoid arthritis; systemic lupus erythematosus; systemic sclerosis.

Publication types

Review

MeSH terms

Animals
Antigens, CD19* / immunology
Autoimmune Diseases* / immunology
Autoimmune Diseases* / therapy
Humans
Immunotherapy, Adoptive* / adverse effects
Immunotherapy, Adoptive* / methods
Receptors, Chimeric Antigen* / genetics
Receptors, Chimeric Antigen* / immunology
Rheumatic Diseases* / immunology
Rheumatic Diseases* / therapy
T-Lymphocytes / immunology
T-Lymphocytes / transplantation

Substances

Receptors, Chimeric Antigen
Antigens, CD19

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Cooperative Research Networks Oriented to Health Results (RICORS), Inflammatory Diseases Network (REI) (RD21/0002/0039; RD24/0007/0016) (JM). Carlos III Health Institute (ISCIII). Next Generation EU funds, which finance the actions of the Recovery, Transformation and Resilience Plan. TerAv RD21/ 0017/0004 (FM) and grant PI21/00298 (FM) funded by Instituto de Salud Carlos III (ISCIII) from the Spanish Ministry of Science and Innovation, by the Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (FEDER), by Consejería de Salud y Familias (CSyF) -Junta de Andalucía - FEDER/European Cohesion Fund (FSE) for Andalucía: Grants: PECART-0031-2020 (FM, JAM). CR-P was funded by Grant PREP2022-000747 funded by MICIU/AEI /10.13039/501100011033 and by ESF+.