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

Author(s)

dos Santos, Matheus Henrique ^[1] ; Machado, Michele Procopio ^[1] ; Kumaresan, Pappanaicken R. ^[2] ; da Silva, Thiago Aparecido ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol & Pathogen Bioagents, BR-14049090 Ribeirao Preto, SP - Brazil

^[2] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 - USA

• Document type: Journal article
• Source: MICROORGANISMS; v. 9, n. 9 SEP 2021.
• Web of Science Citations: 0

Abstract

Cryptococcosis, a systemic mycosis that affects both the immunocompromised and immunocompetent, is caused by the inhalation of dehydrated yeasts or fungal spores of Cryptococcus gattii or Cryptococcus neoformans. The Cryptococcus spp. polysaccharide capsule is composed mainly of glucuronoxylomannan-GXM, its major virulence factor. The capsule thickness increases to more than 15 mu m during titanization, favoring the pathogenesis of cryptococcosis. Previous studies demonstrated that cytotoxic T cells that had been bioengineered with GXM-targeting chimeric antigen receptor (GXMR-CAR) were able to recognize C. neoformans by promoting the control of titanization. GXMR-CAR, a second-generation CAR, contains a single-chain variable fragment that originates from a 18B7 clone: a human IgG4 hinge, followed by a human CD28 (transmembrane/cytoplasmic domains) and a CD3 sigma chain. In the current study, we redirected T cells to target distinct C. neoformans and C. gattii cell types by GXMR-CAR. Lentiviral particles carrying the GXMR-CAR sequence were used to transduce Jurkat cells, and these modified cells interacted with the GXM of the C. gattii R265 strain. Moreover, GXMR-CAR mediated the recognition of C. gattii and C. neoformans yeasts with both thin and thick polysaccharide capsules, and GXMR-CAR Jurkat cells interacted with titan cells sourced from both Cryptococcus spp. Thus, bioengineered cells using CAR can improve the treatment of cryptococcosis. (AU)

• FAPESP's process: 18/18538-0 - Bioengineered of T- and NK-cells by CAR against invasive fungal infections
• Grantee: Thiago Aparecido da Silva
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/09113-6 - Functional activity of T cells modified with GXMR-CAR expressing the intracellular domain of CD28 or CD137, to control of experimental cryptococcosis
• Grantee: Matheus Henrique dos Santos
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/26074-7 - Bioengineered of T- and NK-cells by CAR against invasive fungal infections
• Grantee: Thiago Aparecido da Silva
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 20/11307-3 - Impact of different scFv in GXMR-CAR expressed by T lymphocytes during T-cell activation against Cryptococcus spp
• Grantee: Michele Procópio Machado
• Support Opportunities: Scholarships in Brazil - Master