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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Methods of Controlling Invasive Fungal Infections Using CD8(+) T Cells

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Author(s):
Kumaresan, Pappanaicken R. [1] ; da Silva, Thiago Aparecido [1] ; Kontoyiannis, Dimitrios P. [2]
Total Authors: 3
Affiliation:
[1] Univ Texas MD Anderson Canc Ctr, Dept Pediat, Houston, TX 77030 - USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 - USA
Total Affiliations: 2
Document type: Review article
Source: FRONTIERS IN IMMUNOLOGY; v. 8, JAN 8 2018.
Web of Science Citations: 8
Abstract

Invasive fungal infections (IFIs) cause high rates of morbidity and mortality in immunocompromised patients. Pattern-recognition receptors present on the surfaces of innate immune cells recognize fungal pathogens and activate the first line of defense against fungal infection. The second line of defense is the adaptive immune system which involves mainly CD4(+) T cells, while CD8(+) T cells also play a role. CD8(+) T cell-based vaccines designed to prevent IFIs are currently being investigated in clinical trials, their use could play an especially important role in acquired immune deficiency syndrome patients. So far, none of the vaccines used to treat IFI have been approved by the FDA. Here, we review current and future antifungal immunotherapy strategies involving CD8(+) T cells. We highlight recent advances in the use of T cells engineered using a Sleeping Beauty vector to treat IFIs. Recent clinical trials using chimeric antigen receptor (CAR) T-cell therapy to treat patients with leukemia have shown very promising results. We hypothesized that CAR T cells could also be used to control IFI. Therefore, we designed a CAR that targets beta-glucan, a sugar molecule found in most of the fungal cell walls, using the extracellular domain of Dectin-1, which binds to beta-glucan. Mice treated with D-CAR(+) T cells displayed reductions in hyphal growth of Aspergillus compared to the untreated group. Patients suffering from IFIs due to primary immunodeficiency, secondary immunodeficiency (e.g., HIV), or hematopoietic transplant patients may benefit from bioengineered CAR T cell therapy. (AU)

FAPESP's process: 16/23044-1 - Engineered T cells expressing carbohydrate recognition domain of ArtinM lectin to activate macrophages and treat cryptococcosis
Grantee:Thiago Aparecido da Silva
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor