Redirection of T cells via chimeric antigen receptor (CAR) to control the invasive fungal infections
Swiss Medical Weekly
; 152:34S, 2022.
Article
in English
| EMBASE | ID: covidwho-2040852
ABSTRACT
Invasive fungal infections (IFI) are associated with high rates of morbidity and mortality, and immunocompromised hosts are often affected. Candida albicans is among the main cause of IFIs in the last decades, and Paracoccidioides brasiliensis is found in most of the IFIs identified in the South America. Rhizopus oryzae causes mucormycosis that increased in the COVID-19 pandemic. Host immune response against IFIs depend of the effector activity of T cells, which is compromised in immunodeficient patients. However, chimeric antigen receptor (CAR) technology can redirect T cells to target any antigen inducing the cell activation, which can be applied in immunocompromised patient as done in cell therapy against cancer. We developed a CAR (M-CAR) specific to a carbohydrate on the fungal cell wall, and Jurkat cells expressing M-CAR after lentiviral transduction using a multiplicity of infection (MOI) of 1, 3, 5 or 10 had its recognition capacity evaluated against C. albicans, P. brasiliensis, and R. oryzae. CAR expression increased in a MOI dependent-manner, and M-CAR Jurkat cells produced high levels of IL-2 in the presence of hyphae form of C. albicans,P. brasiliensis yeast, and R. oryzae spores. These findings evidenced the capacity of M-CAR to recognize these fungi inducing T cell activation. This work opened new perspectives to evaluate the fungicidal activity of human T and NK cells expressing M-CAR in response to species of fungi studied. Keywords Chimeric Antigen Receptor (CAR), T cells, invasive fungal infections.
antigen; chimeric antigen receptor; endogenous compound; interleukin 2; adult; bacterial spore; Candida albicans; cell therapy; chimeric antigen receptor T-cell; conference abstract; controlled study; fungal cell wall; fungicidal activity; fungus hyphae; gene expression; human; human cell; immune response; immunocompromised patient; Jurkat cell line; malignant neoplasm; multiplicity of infection; natural killer cell; nonhuman; Paracoccidioides brasiliensis; protein expression; systemic mycosis; T lymphocyte; T lymphocyte activation; yeast
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Swiss Medical Weekly
Year:
2022
Document Type:
Article
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