Stacy Matthews Branch, DVM, PhD
Cancer CAR-T Therapy Adapted to Fight Fungal Infections
Cryptococcus fungi infections can be fatal as the immune system struggles to fight off the invaders, but through CAR-T cell therapy, researchers are seeing positive results
Cryptococcosis, a systemic fungal infection, is caused by the polysaccharide encapsulated yeasts Cryptococcus gatti and Cryptococcus neoformans. The disease can cause pneumonia and meningitis, as well as pathology in other tissues.People can develop cryptococcosis after breathing in one of these fungi, particularly if they are immunocompromised. However, people who are otherwise healthy can also contract the disease. The yeast’s polysaccharide capsule that consists of glucuronoxylomannan (GXM) allows it to evade immune attack by becoming giant cells that can not be phagocytized.
A collaboration of research scientists from the University of São Paulo and the University of Texas developed an immunotherapeutic approach to treat cryptococcosis using CD8+ T cells that target the GMX fungal capsule. The approach entails using the CAR T cell model to develop T cells that express a GXM-specific chimeric antigen receptor (GXMR-CAR). To develop the GXMR-CAR T cells, the researchers transduced human T cells with the GXMR-CAR construct via the use of lentiviral vectors. T-cell expression of GXMR-CAR was determined via flow cytometry. Specificity for GXM was confirmed by detection of GXM interaction with GXMR-CAR+ T cells using GXM-specific antibody.
Lung fungal infection was experimentally induced in laboratory mice by infecting their lungs with C. neoformans yeast via intranasal infusion. The mice were then infused with GXMR-CAR T cells, NoDNA T cells (from mock transduction), or phosphate-buffered saline (PBS). Mouse lung tissue sections were stained, and microscopy showed that there were a lower number of giant fungal cells (titans) in the GXMR CAR T–cell treated group when compared to the NoDNA and PBS groups.
The results of the GXM study suggest that GXMR-CAR T cells can target C. neoformans. Future studies will focus on determining treatment safety and if GXMR-CAR T cells can clear Cryptococcus infection. The possibility of applying the CAR T cell approach to other types of fungal infections can also be considered.
Cancer immunotherapy adapted to fight dangerous fungal infections. (2021). Retrieved 5 April 2021, from https://newatlas.com/medical/cancer-immunotherapy-fungal-infections/
This article was written by free-lance science writer Stacy Matthews Branch, DVM, PhD. It originally appeared on a blog managed by HemaCare, which Charles River acquired in 2020. HemaCare sells biological products such as T cells, stem cells, bone marrow, plasma, and other medical products.