Abstract
Optimizing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through zoledronate pulse stimulation
The Journal of immunology (1950), Vol.196(1_Supplement), pp.143-143.16
05/01/2016
DOI: 10.4049/jimmunol.196.Supp.143.16
Abstract
Abstract Human γδ T cells expressing Vγ2Vδ2 TCRs monitor foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis to mediate immunity to microbes and tumors. Vγ2Vδ2 cells have been used for adoptive cancer immunotherapy with some partial and complete remissions. Most trials have used continuous zoledronate exposure to expand Vγ2Vδ2 cells. Zoledronate inhibits farnesyl pyrophosphate synthase causing isopentenyl pyrophosphate to accumulate that then stimulates Vγ2Vδ2 cells. Because zoledronate exposure is toxic, we hypothesized that a short period of exposure would reduce T cell toxicity but still be sufficient for monocytes uptake. Supporting this, pulse zoledronate exposure with IL-2 resulted in more uniform expansion of Vγ2Vδ2 cells with higher purity and cell numbers as compared with continuous exposure. These Vγ2Vδ2 cells also had higher levels of CD107a and perforin and slightly increased tumor cytotoxicity. Importantly, adoptive immunotherapy with Vγ2Vδ2 cells derived by pulse stimulation controlled human PC-3 prostate carcinoma cells in immunodeficient NSG mice significantly better than those derived by continuous stimulation. Zoledronate pulse stimulation of Vγ2Vδ2 cells in IL-15 also resulted in higher purity and cell numbers. Like with CD8 αβ T cells, IL-15 preserved early memory Vγ2Vδ2 T cell subsets better than IL-2. However, despite this fact, adoptive immunotherapy with Vγ2Vδ2 cells derived in IL-15 showed similar inhibition of PC-3 tumors as those derived in IL-2. Thus, zoledronate pulse stimulation maximizes the purity, quantity, and quality of expanded Vγ2Vδ2 cells. This simple modification to existing protocols could enhance the effectiveness of adoptively transferred Vγ2Vδ2 T cells.
Details
- Title: Subtitle
- Optimizing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through zoledronate pulse stimulation
- Creators
- Mohanad Hameed Nada Al-JanabiHong WangGrefachew WorkalemahuYoshimasa TanakaCraig T Morita
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.196(1_Supplement), pp.143-143.16
- DOI
- 10.4049/jimmunol.196.Supp.143.16
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2016
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984363183902771
Metrics
10 Record Views