Stimulation with lysates of Aspergillus terreus, Candida krusei and Rhizopus oryzae maximizes cross-reactivity of anti-fungal T cells

被引:19
|
作者
Deo, Shivashni S. [1 ,2 ]
Virassamy, Balaji [1 ]
Halliday, Catriona [3 ]
Clancy, Leighton [4 ]
Chen, Sharon [2 ,3 ]
Meyer, Wieland [2 ,3 ,5 ]
Sorrell, Tania C. [2 ,3 ,5 ]
Gottlieb, David J. [1 ,2 ,4 ,6 ]
机构
[1] Westmead Millennium Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
[2] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia
[3] Westmead Hosp, Ctr Infect Dis & Microbiol, Sydney, NSW, Australia
[4] Westmead Hosp, Sydney Cellular Therapies Lab, Sydney, NSW, Australia
[5] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia
[6] Westmead Hosp, Dept Haematol, Blood & Marrow Transplant Unit, Sydney, NSW, Australia
基金
英国医学研究理事会;
关键词
Adoptive T-cell therapy; Aspergillus; Candida; Filamentous fungi; Fusarium; Hematopoietic stem cell transplantation; Invasive fungal disease; Scedosporium; Yeast; Zygomycetes; INVASIVE FUNGAL-INFECTIONS; CLINICAL-SCALE GENERATION; AMPHOTERICIN-B RESISTANCE; TRANSPLANT RECIPIENTS; ACUTE-LEUKEMIA; RISK-FACTORS; EPIDEMIOLOGY; FUMIGATUS; RESPONSES; SUSCEPTIBILITY;
D O I
10.1016/j.jcyt.2015.09.013
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background aims. Invasive fungal diseases caused by filamentous fungi and yeasts are significant causes of morbidity and mortality in immunosuppressed hematology patients. We previously published a method to expand Aspergillus fumigatus specific T cells for clinical cell therapy. In the present study, we investigated expansion of T cells specific for other fungal pathogens and creation of a broadly reactive panfungal T-cell product. Methods. Fungal strains selected were those frequently observed in the clinical hematology setting and included Aspergillus, Candida, Fusarium, Rhizopus and Lomentosporal Scedosporium. Four T-cell cultures specific to each fungus were established. We selected lysates of Aspergillus terreus, Candida krusei and Rhizopus oryzae to expand panfungal T cells. Allelic restriction of anti-fungal activity was determined through the use of specific major histocompatibility complex class II-blocking antibodies. Results. Individual T-cell cultures specific to each fungus could be expanded in vitro, generating predominantly CD4(+) T cells of which 8% to 20% were fungus-specific. We successfully expanded panfungal T cells from the peripheral blood (n = 8) and granulocyte-colony-stimulating factor primed stem cell products (n = 3) of normal donors by using a combination of lysates from Aspergillus terreus, Candida krusei and Rhizopus oryzae. Anti-fungal activity was mediated through human leukocyte antigen (HLA)-DR alleles and was maintained when antigen-presenting cells from partially HLA-DRB1-matched donors were used to stimulate T cells. Conclusions. We demonstrate a method to manufacture panfungal T-cell products with specificity against a range of clinical fungal pathogens by use of the blood and stem cells of healthy donors as the starting material. The safety and efficacy of these products will need to be tested clinically.
引用
收藏
页码:65 / 79
页数:15
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