scholarly journals A Comprehensive Platform for Ex Vivo T-cell Expansion Based on Biodegradable Polymeric Artificial Antigen-presenting Cells

2008 ◽  
Vol 16 (4) ◽  
pp. 765-772 ◽  
Author(s):  
Erin R Steenblock ◽  
Tarek M Fahmy
Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1146-1155 ◽  
Author(s):  
Jennifer D. Bassett ◽  
Teng Chih Yang ◽  
Dannie Bernard ◽  
James B. Millar ◽  
Stephanie L. Swift ◽  
...  

Abstract We have recently reported that CD8+ T-cell memory maintenance after immunization with recombinant human adenovirus type 5 (rHuAd5) is dependent upon persistent transgene expression beyond the peak of the response. In this report, we have further investigated the location and nature of the cell populations responsible for this sustained response. The draining lymph nodes were found to be important for primary expansion but not for memory maintenance, suggesting that antigen presentation through a nonlymphoid source was required. Using bone marrow chimeric mice, we determined that antigen presentation by nonhematopoietic antigen-presenting cells (APCs) was sufficient for maintenance of CD8+ T-cell numbers. However, antigen presentation by this mechanism alone yielded a memory population that displayed alterations in phenotype, cytokine production and protective capacity, indicating that antigen presentation through both hematopoietic and nonhematopoietic APCs ultimately defines the memory CD8+ T-cell response produced by rHuAd5. These results shed new light on the immunobiology of rHuAd5 vectors and provide evidence for a mechanism of CD8+ T-cell expansion and memory maintenance that relies upon both hematopoietic and nonhematopoietic APCs.


2007 ◽  
Vol 123 ◽  
pp. S124-S125
Author(s):  
Roselynn Rodriguez Manzanet ◽  
Jennifer Hartt-Meyers ◽  
Jacqueline Slavik ◽  
Valerie Dardalhon ◽  
Nasim Kassam ◽  
...  

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A812-A812
Author(s):  
Pia Aehnlich ◽  
Per Thor Straten ◽  
Ana Micaela Carnaz Simoes ◽  
Signe Skadborg ◽  
Gitte Olofsson

BackgroundAdoptive cell therapy (ACT) is an approved treatment option for certain hematological cancers and has also shown success for some solid cancers. Still, benefit and eligibility do not extend to all patients. ACT with Vγ9Vδ2 T cells is a promising approach to overcome this hurdle.MethodsIn this study, we explored the effect of different cytokine conditions on the expansion of Vγ9Vδ2 T cells in vitro.ResultsWe could show that Vγ9Vδ2 T cell expansion is feasible with two different cytokine conditions: (a) 1000U/ml interleukin (IL)-2 and (b) 100U/ml IL-2+100U/ml IL-15. We did not observe differences in expansion rate or Vγ9Vδ2 T cell purity between the conditions; however, IL-2/IL-15-expanded Vγ9Vδ2 T cells displayed enhanced cytotoxicity against tumor cells, also in hypoxia. While this increase in killing capacity was not reflected in phenotype, we demonstrated that IL-2/IL-15-expanded Vγ9Vδ2 T cells harbor increased amounts of perforin, granzyme B and granulysin in a resting state and release more upon activation. IL-2/IL-15-expanded Vγ9Vδ2 T cells also showed higher levels of transcription factor T-bet, which could indicate that T-bet and cytotoxic molecule levels confer the increased cytotoxicity.ConclusionsThese results advocate the inclusion of IL-15 into ex vivo Vγ9Vδ2 T cell expansion protocols in future clinical studies.


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