A single dose of CD45-ADC, an investigational targeted therapy being developed to treat different types of autoimmune diseases, is enough to reset the normal function of the body’s immune system in a mouse model of multiple sclerosis (MS), and to delay onset of the disease.
Those findings were presented earlier this week in the poster “Administration of a CD45 Antibody Drug Conjugate as a Novel, Targeted Approach to Achieve Immune System Reset: A Single Dose of CD45-targeted ADC Safely Conditions for Autologous Transplant and Ameliorates Disease in Multiple Models of Autoimmune Disease” (abstract #120), at the American College of Rheumatology (ACR) Annual Meeting in Atlanta, Georgia.
CD45-ADC is an antibody-drug conjugate (ADC) being developed by Magenta Therapeutics in collaboration with Heidelberg Pharma. The medication works by delivering amanitin — a toxic compound that belongs to a group of natural poisons produced by some species of mushrooms — to overactive immune cells containing the CD45 protein on their surface. That destroys them and restores the normal function of the immune system. (Of note, the CD45 protein is typically found on immune cells and stem cells.)
For that reason, CD45-ADC is currently being explored as a new form of targeted therapy for several autoimmune diseases, including MS.
New findings presented at the ACR meeting showed that in mice with experimental autoimmune encephalomyelitis (EAE, a mouse model of MS), a single dose of CD45-ADC was sufficient to eliminate overactive immune cells, and to restore the normal function of the animals’ immune systems.
Moreover, investigators reported that treatment with CD45-ADC, followed by a stem cell transplant to repopulate the animals’ bodies with healthy immune cells, delayed the disease onset and halted the progression of disease activity in EAE mice.
According to the research team, immune reset through stem cell transplant — in which disease-causing cells are replaced by healthy cells to rebuild the immune system — has been shown to induce durable remission in patients with autoimmune diseases, including MS.
Given the encouraging results in animal models, the team “developed an anti-human CD45-ADC that cross-reacts with non-human primates (NHP). Substantial depletion of both lymphocytes [white blood cells] and hematopoietic [blood] stem cells (HSCs) was observed at well-tolerated doses,” the researchers wrote.
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