Promising cancer immunotherapy target also supports new blood vessel formation

A paper entitled, IDO1 is an Integral Mediator of Inflammatory Neovascularization, published in the December edition of EBioMedicine, focuses on IDO1, an enzyme that is overexpressed in many different cancers. Thus far, IDO1 has been of interest because of its ability to promote tumor development by dialing back local immune responsiveness.

Two of the researchers at the [[www.mainlinehealth.orgLankenau Institute for Medical Research, (LIMR) associate professor Alexander Muller, and CEO George Prendergast, have been at the forefront of establishing IDO1 as an important immuno-oncology therapeutic target, an idea that has gained the attention of pharmaceutical companies and cancer clinicians.

Reevaluating current data and development strategies

Indeed, there are now multiple IDO1 inhibitors being evaluated in clinical trials for cancer patients, the inception of which are rooted in the LIMR researchers’ earlier work. Although research into IDO1’s immune-regulatory activity has snowballed, these new findings provide a wholly unrecognised insight into how IDO1 inhibitors may benefit cancer patients, and could lead biomedical researchers to reevaluate current clinical data and development strategies.

Typically, this would not even be a consideration for conventional chemotherapeutic agents due to their general toxicity; however, the safety profile of IDO1-inhibitory drugs has been shown to be quite good, notes Muller.

Treatment of neovascularisation

However, the report adds a completely new dimension to the overall understanding of IDO1’s role in disease, demonstrating it is an integral player acting at the regulatory interface between key inflammatory cytokines that control the process of abnormal blood vessel formation referred to as neovascularisation.

“This discovery is important because work in the angiogenesis field has established neovascularisation as one of the essential hallmarks of tumor development,” he says. “So to find a mechanism, notably IDO1 inhibition, that — in addition to overcoming immune escape — can also reduce neovascularisation is an exciting discovery with far-reaching therapeutic implications.”

Potential for treating retinopathies

Along these lines, the EBioMedicine report provides compelling evidence that retinopathies may respond well to treatment with an IDO1 inhibitor. Retinopathy is associated with abnormal blood vessel formation, and currently the most effective way to treat this condition is with direct injections of a therapeutic antibody into the eyes.

In this context, the development of an eyedrop formulation of a small molecule IDO1 inhibitor could present an attractive alternative for the treatment of major ocular diseases, such as diabetic retinopathy and wet macular degeneration.