| Autor: |
Justin C, Boucher, Bin, Yu, Gongbo, Li, Bishwas, Shrestha, David, Sallman, Ana Marie, Landin, Cheryl, Cox, Kumar, Karyampudi, Claudio, Anasetti, Marco L, Davila, Nelli, Bejanyan |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Journal of Immunotherapy. 46:5-13 |
| ISSN: |
1524-9557 |
| Popis: |
Higher γδ T cell counts in patients with malignancies are associated with better survival. However, γδ T cells are rare in the blood and functionally impaired in patients with malignancies. Promising results are reported on the treatment of various malignancies with in vivo expansion of autologous γδ T cells using zoledronic acid (zol) and interleukin-2 (IL-2). Here we demonstrated that zol and IL-2, in combination with a novel genetically engineered K-562 CD3scFv/CD137L/CD28scFv/IL15RA quadruplet artificial antigen-presenting cell (aAPC), efficiently expand allogeneic donor-derived γδ T cells using a Good Manufacturing Practice (GMP) compliant protocol sufficient to achieve cell doses for future clinical use. We achieved a 633-fold expansion of γδ T cells after day 10 of coculture with aAPC, which exhibited central (47%) and effector (43%) memory phenotypes. In addition,90% of the expanded γδ T cells expressed NKG2D, although they have low cell surface expression of PD1 and LAG3 inhibitory checkpoint receptors. In vitro real-time cytotoxicity analysis showed that expanded γδ T cells were effective in killing target cells. Our results demonstrate that large-scale ex vivo expansion of donor-derived γδ T cells in a GMP-like setting can be achieved with the use of quadruplet aAPC and zol/IL-2 for clinical application. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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