A single dose of an engineered antibody known as CD45-ADC can effectively eliminate disease-causing immune cells and ease the symptoms of scleroderma in mice, studies show.
CD45-ADC is an example of Magenta Therapeutics‘ efforts to develop targeted antibody-drug conjugates (ADCs) to specifically remove disease-causing cells from the body and reset the overall immune response without the need for chemotherapy or radiation.
“Millions of patients worldwide live with debilitating autoimmune diseases, with no options for curative therapy,” John Davis, MD, chief medical officer of Magenta, said in a press release. “Magenta is developing targeted medicines such as CD45-ADC to enable more patients with autoimmune diseases to undergo a one-time, curative immune reset.”
The latest data, “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.” were presented at the 2019 American College of Rheumatology and Association of Rheumatology Professionals (ACR/ARP) Annual Meeting, held in Atlanta, Georgia.
Hematopoietic stem cell transplant (HSCT) using the patient’s own cells (autologous transplant) is a highly effective treatment strategy for several autoimmune diseases, including scleroderma and multiple sclerosis.
This approach can induce long-term disease remission because it eliminates autoreactive immune cells. At the same time, it re-establishes a self-tolerant, healthy immune system.
Its therapeutic potential made the European League Against Rheumatism (EULAR) recommend the strategy in the guidelines for scleroderma treatment. However, only a small fraction of eligible patients undergo autologous HSCT, in part due to toxicity associated with current immune-depleting (conditioning) protocols.
Magenta engineered CD45-ADC as a single conditioning agent to overcome this limitation. This antibody specifically targets the protein CD45, which is present in immune and hematopoietic stem cells. When it binds to its target, the therapy releases the toxin amanitin to induce cell death.
Researchers tested the therapeutic activity of CD45-ADC in mice with scleroderma-like disease.
Results revealed clear resolution of disease-related skin manifestations and regrowth of hair after a single dose of the therapy. In contrast, animals receiving a placebo did not show such benefits.
Treatment with CD45-ADC also led to a durable cell depletion, maintaining low levels of disease-associated immune T-cells for up to 62 days.
Experiments in mouse models of multiple sclerosis and rheumatoid arthritis further supported the ability of CD45-ADC to induce immune reset and halt disease progression with only one administration.
“Targeted CD45-ADCs may represent a safer and better tolerated approach for conditioning patients prior to immune reset … and significantly reduce the side effects associated with current conditioning,” the researchers wrote.
“The data presented at ACR provide important proof of concept for our immune reset platform across a broad range of diseases, including multiple sclerosis and systemic sclerosis [or scleroderma],” Davis said. “We expect to declare a development candidate and progress this medicine into [clinical trials]-enabling studies next year as we work to allow more patients to live their lives without autoimmune disease.”
In addition, Magenta exercised its option with Heidelberg Pharma for exclusive worldwide rights for ADCs using amanitin and targeting CD45. Heidelberg Pharma will be paid an undisclosed milestone payment, according to the press release.