Abundance of T Stem Cell Memory in F-CAR-T Cells CausingYounger Phenotypes

Authors

  • Xing Huang

DOI:

https://doi.org/10.61173/g63sfg45

Keywords:

T stem cell memory, RAJI, F-CAR-T cells, Flow cytometry, PD-1+LAG3+Tim3+ T-cells, CD45RO-, CD62L+, SCFV

Abstract

This study will introduce a novel anti-CD19 CAR-T technology – FasT CAR-T (F-CAR-T)- shortens production time,
increases production quality, and produces healthier T cells with a younger phenotype. This study also investigates the
effect of the abundance of T stem cell memory in F-CAR-T cells’ correlation with younger phenotypes, leading to better
persistence in T cells by manipulating the number of Car T cells injected into Raji xenografts. Using mouse cell lines,
RAJI xenograft models, and F-CAR-T cells, this study will measure cell proliferation of Tscm, CD45RO-, CD62L+,
and PD1/Lag3/Tim3 by flow cytometry and count Car expressing cells using SCFV antibodies. The experiment results
will show if F-CAR T cells have significantly greater expansion and T stem cell memory than C-CAR-T cells. The
C-CAR-T cells with less exhaustion, indicating the effect of T stem cell memory distinguishing F-CAR-T therapy from
conventional CAR-T therapy. The result of this study will provide critical information for the future clinical trial of
F-CAR-T cell therapy. This work can inspire to utilize the T stem cell memory, which exhibits great antitumor activity,
to explore the mechanism of modulation of CAR-T cell metabolism and T cell differentiation.

References

[1] Yang, J., He, J., Zhang, X. et al. Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study. Blood Cancer J. 12, 104 (2022). https://doi.org/10.1038/s41408-022-00694-6

[2] Zhang, C., He, J., Liu, L. et al. Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia. Blood Cancer J. 12, 96 (2022). https://doi.org/10.1038/ s41408-022-00688-4

[3] Simon S, Labarriere N. PD-1 expression on tumor-specific T cells: Friend or foe for immunotherapy? Oncoimmunology. 2017 Sep 14;7(1):e1364828. doi: 10.1080/2162402X.2017.1364828. PMID: 29296515; PMCID: PMC5739549.

[4] Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010 Sep 27;207(10):2187-94. doi: 10.1084/ jem.20100643. Epub 2010 Sep 6. Erratum in: J Exp Med. 2011 Jun 6;208(6):1331. PMID: 20819927; PMCID: PMC2947065.

[5] Gattinoni L, Speiser DE, Lichterfeld M, Bonini C. T memory stem cells in health and disease. Nat Med. 2017 Jan 6;23(1):18- 27. doi: 10.1038/nm.4241. PMID: 28060797; PMCID: PMC6354775.

[6] Front. Immunol., 28 April 2022 Sec. Cancer Immunity and Immunotherapy. https://doi.org/10.3389/fimmu.2022.878209

[7] Liu Y, Chen X, Han W, Zhang Y. Tisagenlecleucel, an Approved Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Leukemia. Drugs Today (2017) 53:597. doi: 10.1358/dot.2017.53.11.2725754

[8] Fan J, Das JK, Xiong X, Chen H, Song J. Development of CAR-T Cell Persistence in Adoptive Immunotherapy of Solid Tumors. Front Oncol (2021) 10:574860. doi: 10.3389/ fonc.2020.574860

Downloads

Published

2023-06-01