Glucuronoxylomannan (GXM)

Glucuronoxylomannan (GXM) is the primary capsular polysaccharide of the pathogenic fungi Cryptococcus neoformans and Cryptococcus gattii, accounting for approximately 90% of the capsule's mass [2, 4]. It is a high-molecular-weight, branched polymer essential for fungal virulence and survival within the host [2, 5]. GXM functions as a potent immunomodulator, facilitating immune evasion by inhibiting phagocytosis, suppressing T-cell proliferation, and modulating cytokine profiles toward an anti-inflammatory state [1, 13, 16]. In clinical settings, the detection of GXM in serum or cerebrospinal fluid serves as the gold-standard biomarker (CrAg test) for diagnosing cryptococcosis [3, 13]. As a therapeutic target, GXM is the focus of various strategies, including monoclonal antibodies like mAb 18B7, conjugate vaccines, and experimental CAR T-cell therapies [8, 11, 14]. These interventions aim to neutralize the polysaccharide's suppressive effects or enhance the clearance of the encapsulated yeast [8, 13]. However, the shedding of large amounts of soluble GXM into host tissues and fluids presents a significant challenge for targeted therapies [8, 12].

Other names

Cryptococcal capsular polysaccharideCryptococcal antigenCrAgGXM

Therapeutic strategies involve the neutralization of the capsular polysaccharide to prevent immune suppression, opsonization to enhance phagocytic clearance, and direct fungal cell lysis through engineered CAR T-cell recognition [8, 11, 13].