# Offsetting CNS inflammatory damage with anti-CXCR3 antibody immunotherapy > **NIH VA I21** · VETERANS HEALTH ADMINISTRATION · 2024 · — ## Abstract Cryptococcus neoformans: is an environmental fungal pathogen that causes substantial morbidity and mortality worldwide, recently named among 4 critically important fungal pathogens on the WHO global priority list. Veterans are at increased risk of cryptococcosis due to higher-than-average rates of conditions associated with immune compromise. The CDC estimates nearly 200,000 deaths per year are attributable to C.n. infection with almost all related to cryptococcal dissemination to the central nervous system CNS, resulting in fatal cryptococcal meningoencephalitis (CM). The survivors frequently develop disabilities due to CNS damage. There is increasing evidence these paradoxical responses to therapy are mediated by patients own immune response to the fungus, further supported by the beneficial effects of anti-inflammatory therapy. We reported that CXCR3+,Th1 T-cells represent a pathological cell subset that is dispensable for clearance of CM and propose that interception of CXCR3-pathway with anti-CXCR3 antibody (Ab) therapy will create a “protective shield” for neurons and significantly reduce the inflammatory damage in patients with fungal and possibly other types of CNS infections known to trigger the inflammatory CNS damage. Our preliminary data support highly beneficial role of anti-CXCR3-Ab therapy in mouse model of CM but these novel findings need to be validated before anti-CXCR3-Ab can be considered for clinical trials. Our goal is to validate that to demonstrate pre- clinically that this therapeutic strategy could be a viable option for the treatment/ prevention of inflammatory CNS injury that occurs during CNS infections. The proposed 2-year project will assess and validate beneficial effects of anti-CXCR3 antibody therapy in using 3 mouse models of CM that show different scope of fungal virulence or inflammatory response, alone, and in the settings of standard antifungal therapy used in patients with CM. Aim 1: To validate effects of anti-CXCR3 antibody treatment on the development of CNS symptoms and inflammatory pathology in models of models of murine CM. a) To evaluate benefits of anti-CXCR3 treatment in a highly inflammatory model of mouse CM with strain 52D. b) To evaluate effects anti-CXCR3 treatment in a balanced inflammation model of mouse CM with strain 184A c) To evaluate effects of anti-CXCR3 treatment in progressive model of mouse CM with strain H99 Aim 2: To validate effects of anti-CXCR3 antibody treatment in combination with standard of care anti- cryptococcal drug therapy. The inflammatory brain injury can occur despite the standard treatment with antifungal drugs in both human patients and in our mouse model. These studies will determine if beneficial effects of CXCR3-neutralization would be synergized when combined with antifungal therapy using following approaches: a) To evaluate benefits of anti-CXCR3 therapy in CM models with strains 52D, 184A, and H99 in combination with the liposomal Amphotericin B. b) T... ## Key facts - **NIH application ID:** 10805718 - **Project number:** 1I21BX006349-01 - **Recipient organization:** VETERANS HEALTH ADMINISTRATION - **Principal Investigator:** Michal A Olszewski - **Activity code:** I21 (R01, R21, SBIR, etc.) - **Funding institute:** VA - **Fiscal year:** 2024 - **Award amount:** — - **Award type:** 1 - **Project period:** 2024-01-01 → 2025-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10805718 ## Citation > US National Institutes of Health, RePORTER application 10805718, Offsetting CNS inflammatory damage with anti-CXCR3 antibody immunotherapy (1I21BX006349-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10805718. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*