Combining Immunotherapy With Fungal Therapeutics: The Future of Treatment?

This is a short series discussing fungal infections including newer treatment concepts, the distinct geography of clades and the increasing spread of Candida auris, and insights around developing therapeutics for fungal infections.

There are inherent challenges in developing therapeutics for fungal infections, explains Jatin Vyas, PhD, MD, professor of Medicine, Columbia University, associate dean for Academic Innovation, and director of Physician- Scientist Programs at the Vagelos Institute for Biomedical Research Education.

“Unlike antibacterials, bacteria being a prokaryotic organism, fungi are eukaryotic organisms. And what does that mean? They're closer to the cellular structure to mammals than they are to bacteria. They have an enclosed nucleus. They have many of the enzymatic machinery that closely mimics what we have as mammals. And so the challenge is that the targets that we can use are actually considerably smaller,” said Vyas. “There's many agents that can treat fungal organisms, the problem is they have unacceptable side effects, because those are the same mechanisms that our body uses for normal metabolism and normal life. And so the world where we can find distinctions between here's something that a fungal organism is using, like Canada auris, but is not operational in mammalian cells, is actually relatively small, and so that limits the number of targets that we have available, and that becomes a significant challenge in terms of finding better antifungals.”

Lessons from Immunotherapy

One of the novel concepts emerging in fungal infection treatment is the idea of taking immunotherapy and combining it with fungal infections. As an example, Vyas notes a recently published article in the New England Journal of Medicine, that details the case of a young patient who had disseminated coccidiomycosis. Investigators identified issues that were going on with that patient’s immune system, and they were able to skew the child’s immune system in one direction to another direction, he said.

“In combination with antifungals, they were able to affect a cure where antifungals for a year were not capable…so this leads to this concept that if we could harness the power of the immune system and combine it with antifungals, we may have the best shot of curing patients,” Vyas said.

He says there is a significant parallel in looking at how they are successfully treating cancer today and potentially applying it to infectious disease.

“If we can combine immunotherapy with cancer chemotherapy, we oftentimes can see a significant improvement in those patients’ response rates as well as survival. And so we're taking a page out of that oncology part and now applying this to infectious disease. Hopefully we will get to a point where, in the future, infectious disease physicians will both identify the organism, let's say, in this particular situation, a patient with Candida auris, identify what is the right antifungal, and then try to identify what are the ways by which we can boost the immune system in that particular patient so that they can affect a cure and therefore decrease their morbidity and mortality associated with these invasive fungal infections.”

In the next episode, Vyas talks about Candida auris including geographic clades and insights around its spread.