Upregulating the Expression of F-CAR-T Cells by Increasing theAmount of Tcm Cells in F-CAR-T Cells
DOI:
https://doi.org/10.61173/p3whn313Keywords:
Tscm cell, CD19 expressing RAJI, CAR-T cellAbstract
CAR-T cells are most known for protecting one’s immune system by attacking cancer cells. Usually, it is infused into
the patient’s body to provide treatment. When comparing F-CAR-T cells with C-CAR-T cells, F-CAR-T cells typically
have more Tscm cells. Thus, this study investigates the effect of upregulating Tscm cells in F-CAR-T cells using FACS
for CD45RO- and CD62L+. The experiments will use the expression of Tim3, LAG3, and PD1 and measure if F-CAR-T
cells can kill CD19-expressing RAJI cells by FACS for CD19 and Annexin V/PI through various durations and with
various numbers of injected CarT. Then Tscm cells are measured by FACS for CD45RO- and CD62L+. Moreover,
two special diets will be used as an experimental control to regulate the increase and decrease of Tscm cells. There are
two most possible results: (1) Both the Tscm receptor and the diet will have a positive effect in terms of upregulating
Tscm cells in F-CAR-T cells; (2) Both the mouse peritoneal macrophage and the diet will inhibit the growth of Tscm
cells. The result of our study will provide important information for the future clinical trial of Tscm cell application and
improve CAR-T cells’ persistence. Future studies should focus on shortening the CAR-T cells manufacturing processes
as well as exploring more applicable usages of Tscm cells in detail
References
[1] Flynn JK, Gorry PR. Stem memory T cells (TSCM)- their role in cancer and HIV immunotherapies. Clin Transl Immunology. 2014 Jul 18;3(7): e20. doi: 10.1038/cti.2014.16. PMID: 25505968; PMCID: PMC4232066.
[2] Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017; 129:3322–31.
[3] Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N. Engl J Med. 2018; 378:449–59.
[4] Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisa-genlecleucel in children and young adults with B-cell lymphoblastic leukemia. NEngl J Med. 2018; 378:439–48.
[5] Pietrobon, V.; Todd, L.A.; Goswami, A.; Stefanson, O.; Yang, Z.; Marincola, F. Improving CAR T-Cell Persistence. Int. J. Mol. Sci. 2021, 22, 10828.
[6] Chakravarti N, Prieto VG. Predictive factors of activity of anti-programmed death-1/programmed death ligand-1 drugs: immunohistochemistry analysis. TransI Lung Cancer Res 2015; 4(6): 743-751. Doi: 10.3978/j.issn.2218-6751.2015.12.10
[7] Tumaini B, Lee DW, Lin T, Castiello L, Stroncek DF, Mackall C, et al. Simplified process for the production of anti- CD19-CAR-engineered T cells. Cytotherapy 2013; 15:1406–15.
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