How ABBV-181 works
ABBV-181 is a type of immunotherapy; it aims to improve the immune response against cancer rather than targeting the tumor directly, allowing the body itself to fight the tumor.
The immune system is normally capable of directing a type of immune cell, called a T-cell, to recognize and attack abnormal cells that are expressing a specific antigen. An antigen is a substance that is not normally found in the body. Cancer cells frequently over-produce such antigens, but they also have ways to evade detection by the immune system and can grow unchecked.
Several “immune system checkpoints” are in place to inactivate T-cells so they do not accidentally attack healthy cells. These checkpoints are essential to preventing damage to healthy tissues. One such immune system checkpoint is called the programmed cell death-1 (PD-1) pathway.
PD-1 is a protein found on the surface on T-cells. When this T-cell protein binds to the ligand PD-L1, a protein that is normally only produced by healthy cells, it sends a signal to the T-cell to not attack. Some cancers hijack this pathway system by producing PD-L1 on their cells, tricking T-cells into “thinking” that they are healthy cells.
ABBV-181 is an antibody, a protein designed to interact with a target, against PD-1. By binding to PD-1, ABBV-181 blocks the interaction between PD-1 and PD-L1. This prevents the inhibitory signaling pathway from being triggered when the T-cell encounters the tumor. In other words, it intends to restore the immune system’s ability to recognize tumor cells as abnormal, allowing T-cells to target these tumor cells for death.
Through this mechanism, ABBV-181 should allow the immune system to prevent further tumor growth, and may even result in a reduction in tumor size.
ABBV-181 in clinical trials
AbbVie has initiated an open-label Phase 1 study (NCT03000257) to investigate ABBV-181 alone or in combination with rovalpituzumab tesirine. The trial will have two parts: a monotherapy, dose-escalation part to determine the maximum tolerated dose of ABBV-181 for future clinical studies and to assess its safety and tolerability. The trial’s second part will investigate ABBV-181 as a combination therapy with rovalpituzumab tesirine, another investigational anti-cancer compound being developed by AbbVie.
The trial aims to recruit 182 people with advanced solid tumors at multiple sites across the U.S, Australia, Canada, France, Spain, and Japan. It is set to run through December 2019.
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