Adapting Immunotherapy solutions to fight fungal infections

Infections of Cryptococcus fungi are potentially fatal, because the immune system has a hard time fighting off the invaders. But researchers have given it a helping hand, by adapting a cancer immunotherapy technique called CAR T cell therapy.

The immune system is our first, and in many ways best, line of defense against disease. Immune cells patrol our bodies for signs of pathogens, whether they be rogue cells at risk of becoming cancerous, or foreign invaders like bacteria, viruses and fungi.

Unfortunately, many of these pathogens develop ways to evade detection or destruction, so the emerging field of immunotherapy aims to return the upper hand to the immune system. One of the most promising forms is chimeric antigen receptor (CAR) T cell therapy, where the immune system’s T cells are extracted, engineered to better home in on a specific target, then returned to the body.

CAR T cell therapy has already been approved by the FDA for human use in the US, to treat cancers like leukemia and lymphoma. But scientists are increasingly investigating how to extend its use to other diseases, such as clearing out dormant viral reservoirs in HIV patients or to fight off rogue T cells that damage insulin-producing cells in the pancreas, thereby preventing diabetes from developing.

For the new study, researchers at the University of São Paulo and the University of Texas adapted CAR T cell therapy to treat fungal infections. They focused on two infectious species of Cryptococcus, C. gattii and C. neoformans, which can cause meningitis or meningoencephalitis and are potentially fatal infections, particularly for people with compromised immune systems.

These fungi are tricky for the immune system to clear out on its own, thanks to a capsule that it wraps itself in as a defense mechanism. For the new study, the researchers adapted the CAR T cells to target a polysaccharide called GXM, which the fungi use to build this capsule.

In lab culture tests, the team found that the engineered CAR T cells were able to bind to cells treated with GXM. Next, they were able to interact with the yeast form of C. neoformans, containing the growth of the fungus and reducing the number of the cells that help it spread.

The team says that these results indicate that CAR T cell therapy could be a good treatment for fungal infections, not just of Cryptococcus but other species such as Candida albicans and Histoplasma capsulatum.

The next steps will involve tests in animal models of these infections. There’s also the hurdle of CAR T cell therapy turning deadly in some cases, which could put render these kinds of treatments far too risky for some diseases. However, other studies are investigating ways to make it safer.