Mechanism of Action of first in class Fully Human Anti-ThymoGlobulin experimental Drug (SAB-142) as a Treatment Option for Type 1 Diabetes — 11a — Olivia Allen, Quincee Simonson

Type 1 Diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β cells. People with T1D have a life-long dependence on exogenous insulin. Anti-ThymoGlobulin (ATG) is immunoglobulin fraction of serum from animals immunized with human thymocytes; it is composed of antibodies raised against a variety of surface lymphocyte markers. The general mechanism of ATG action is immunosuppression by the means of temporal lymphodepletion. As T1D is caused by hyperactivation of self-reactive T lymphocytes that kill β cells, it is logical to suggest that transient lymphodepletion by ATGs might be beneficial. 

According to Haller et al, (2019) a single administration of low-dose ATG to T1D patients partially preserved β cell function for up to 2 years. Animal ATGs, however, cannot be re-dosed without serious risk of anaphylaxis. which is caused by the severe allergic reaction following repeated administration of xenobiotic agents of animal origin (antibodies). Therefore, we hypothesized that an agent possessing beneficial effects of the current animal ATGs, but lacking risk of xenobiotic responses would be significantly advantageous for prolonged β cell preservation in T1D setting. 

The first in class fully human ATG drug – SAB-142 is produced in transchomosomal bovine that has human Ig locus inserted into their genome. Here, we will test SAB-142 using rabbit ATG (rATG, Thymoglobulin®) as an active comparator. My objective is to uncover the specific mechanism of action of SAB-142 in comparison to rATG. Specifically, we will expose peripheral blood mononuclear cells (WBC) from healthy volunteers and T1D patients to SAB-142 and rATG and perform single-cell RNA sequencing to identify changes induced by the drugs.

Sanford Research
Alexei Savinov