Abstract

Autoimmune diseases are disorders caused by distorted immune reactions to own antigens and result in prolonged inflammation and tissue destruction. Although there has been improvement in immunosuppressive therapy, treatment in most cases is usually unspecific, thus proving to be ineffective with a numerous side effects. A paradigm shift comes in the form of translational immunotherapy, which links basic innate immunological insights to translational, patient-specific, clinical intervention. This review discusses recent developments in translational immunotherapy of autoimmune diseases, covering the full spectrum in the translational pipeline between target discovery and the generation of patient-specific therapies. We identify some important discoveries in immune tolerance, antigen specific immune control, and molecular mechanisms of autoimmunity. Approaches combining high-throughput omics technologies, including genomics, proteomics, and single-cell sequencing have enabled novel biomarker and therapeutic target identification across autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. Moreover, breakthroughs in bioengineering have led to the creation of design precision biologics that target specific innateness pathways in the immune system, such as monoclonal antibodies, genetically engineered T-cells, and tolerogenic vaccines that can uniquely restrain virulent lineages of the immune response without compromising overall immune fitness. It also reviews how the personalized medicine paradigm can be used in predicting the response to treatment and the fine-tuning of therapy to respond to individual immunological fingerprints, notably through the use of personalized medicine methods such as the use of patient-derived organoids, as well as immune profiling. Immune heterogeneity, off-target effects, and regulatory challenges are covered as well as the new strategies of dealing with them. Lastly, we have proposed the integrative clinical trial design based on the real-time monitoring of biomarkers and using adaptive protocols to enhance the clinical development of potential immunotherapies. Translational immunotherapy could change the face of the treatment of autoimmune diseases by creating safer, more efficient, and personalized therapy approaches by combining mechanistic information and new therapeutic platforms in research

Key words: Autoimmune diseases, translational immunotherapy, target discovery, personalized medicine, immune tolerance, biologics, immune profiling, patient-specific therapies.