Nicola Ferrari, Director of Translational Science Lead for Respiratory and Immunology at AstraZeneca, shared a post on LinkedIn:
“Immune reset and immune retune: approaching cure?
- The emergence of potent depletion therapies for the treatment of refractory autoimmunity has led to the concept of immune reset.
- Understanding whether immune reset equates to cure, and whether cure is achievable through non-depleting approaches, depends on the identification of immune biomarkers for measuring healthy and pathological immunity.
- A current limitation of the field is the inability to identify and specifically eradicate disease-causing B cell clones. Conceptually, the equivalent of oncological ‘minimal residual disease’ is the goal, but with a focus on autoreactive B lineage cells rather than malignant cells. Without robust biomarkers of autoreactivity, ‘cure’ must remain a clinical concept that is impossible to diagnose with certainty.
- Non-depleting therapies, which have fewer potential hazards than cell depletion, could achieve reset. Regulatory CAR T cell therapy could be an option and many therapies are being developed to tolerize autoreactive T cells. These therapies are mostly non-depleting and might be considered to ‘retune’ rather than ‘reset’ the immune system.
- The emergence of deep B cell depletion might signal a turning point in the management of at least some autoimmune diseases. As with all therapeutic revolutions, small-scale clinical trials must be accompanied by cutting-edge translational research and experimental medicine.
- Ultimately, head-to-head trials of different therapies will be needed to demonstrate their relative efficacy and safety and the optimal management of relapse.
- Improved understanding of autoreactivity and immune homeostasis, with the development of companion biomarkers, will hopefully be a consequence of this field. This understanding should facilitate the development of a range of therapies that can achieve immune reset or immune retune and, ultimately, provide an objective definition of cure.”
Title: Immune reset and immune retune: approaching cure?
Author: John D. Isaacs
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