Glucuronoxylomannan in the Cryptococcus species capsule as a target for Chimeric Antigen Receptor T-cell therapy

Titan Cells and Yeast Forms of Cryptococcus neoformans and Cryptococcus gattii Are Recognized by GXMR-CAR

“…The design and construction of GXMR-CAR to target Cryptococcus spp. was reported by da Silva et al [ 17 ]. The GXM-binding domain localized in the extracellular portion consists of a single-chain variable fragment (scFv) of the anti-GXM mAb 18B7 clone, which was generated by Casadevall et al [ 19 ].…”

“…This polysaccharide results in small differences in the monosaccharide composition of Cryptococcus spp. In the current study, we evaluated the capacity of GXMR-CAR to bind to the GXM of C. gattii R265; as reported by da Silva et al, GXMR-CAR interacts with GXM of C. neoformans H99 [ 17 ]. To investigate the recognition of the GXM in C. gattii R265 by GXMR-CAR, lentiviral particles carrying the GXMR-CAR sequence were used to transduce Jurkat cells, generating a stable GXMR-CAR Jurkat cell line.…”

“…To investigate the recognition of the GXM in C. gattii R265 by GXMR-CAR, lentiviral particles carrying the GXMR-CAR sequence were used to transduce Jurkat cells, generating a stable GXMR-CAR Jurkat cell line. The GXM of C. gattii R265 was incubated with the GXMR-CAR Jurkat cells, and the interaction between GXM and GXMR-CAR was detected using an approach that was previously reported by da Silva et al [ 17 ], which is presented in Figure 1 . GFP-labeled GXMR-CAR Jurkat cells interacted with soluble GXM, as detected by murine anti-GXM antibody, followed by biotin-labeled goat anti-mouse IgG and streptavidin-PE.…”

“…[ 15 , 16 ]. The titanization process can be controlled by cytotoxic T cells using an engineered chimeric antigen receptor (CAR) that targets GXM expressed on the cell surface of C. neoformans , as reported by da Silva et al [ 17 ]. The authors demonstrated that T cells expressing a GXM-specific CAR (GXMR-CAR) containing a single-chain variable fragment from a 18B7 clone were able to target GXM, decreasing the percentage of titan cells at the C. neoformans infection site.…”

“…The present study determined whether GXMR-CAR, a second-generation CAR that contains a modified human IgG4 hinge, followed by a human CD28 (transmembrane and cytoplasmic domains) and a CD3ς chain [ 17 ], could redirect T cells to target distinct C. neoformans and C. gattii cell types in a Jurkat cell line. We demonstrated that Cryptococcus spp.…”