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Antigen-specific CD8+ memory stem T cells generated from human peripheral blood effectively eradicate allogeneic targets in mice.
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ABSTRACT: Background
As the implantation and long-term existence of tumor-specific T cells in host are the prerequisite for adoptive immunotherapy, memory stem T cells (TSCM) with self-renewal and differentiation capacity show the greatest potential to implant and long-term exhibit function in vivo, compared with other T cells of differentiation stages. Hence, tumor-specific TSCM have become potential candidate for adoptive T cell therapy of cancer. Here, we reported a protocol to generate allogeneic antigen-specific CD8+ TSCM cells from human PBLs.Methods
To prepare allogeneic antigen-specific CD8+ TSCM, we used an LCL named E007 of defined HLA allotyping as simulator, a co-culture of E007 and allogeneic PBLs was carried out in the presence of differentiation inhibitor TWS119 for 7?days. Sorting of proliferation cells ensured the E007-specificity of the prepared TSCM cells. The sorted lymphocytes underwent further expansion by cytokines IL-7 and IL-15 for further 7?days, making the E007-specific CD8?+?TSCM expanded in number. The stem cell and T memory cell properties of the prepared CD8+ TSCM were observed in NOD-SCID mice.Results
Our protocol began with 1?×?107 PBLs and resulted in 2?×?107 E007-specific CD8+ TSCM cells in 2?weeks of preparation. The prepared TSCM cells exhibited a proliferative history and rapid differentiation into effector cells upon the E007 re-stimulation. Importantly, the prepared TSCM cells were able to exist long and reconstitute other T cell subsets in vivo, eradicating the E007 cells effectively after transferred into the LCL burden mice.Conclusions
This protocol was able to prepare allogeneic antigen-specific CD8+ TSCM cells from human PBLs. The prepared TSCM showed the properties of stem cells and T memory cells. This study provided a reference method for generation of antigen-specific TSCM for T cell adoptive immunotherapy.
SUBMITTER: Guan L
PROVIDER: S-EPMC6286512 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Antigen-specific CD8+ memory stem T cells generated from human peripheral blood effectively eradicate allogeneic targets in mice.
Stem cell research & therapy 20181207 1
<h4>Background</h4>As the implantation and long-term existence of tumor-specific T cells in host are the prerequisite for adoptive immunotherapy, memory stem T cells (T<sub>SCM</sub>) with self-renewal and differentiation capacity show the greatest potential to implant and long-term exhibit function in vivo, compared with other T cells of differentiation stages. Hence, tumor-specific T<sub>SCM</sub> have become potential candidate for adoptive T cell therapy of cancer. Here, we reported a protoc ...[more]
