Objective:

Since T memory stem cell (TSCM) is a kind of cell with strong self-renewal ability, long-term persistence, proliferation ability and anti-tumor activity, and is an ideal candidate cell for cancer immunotherapy. We aimed to explore the amount of TSCM cells in multiplt myeloma(MM) and the established a method to expansion TSCM in vitro, and to further explore the effect of CAR-T cells prepared by TSCM on MM cells.

Methods:

TSCM cells (CD45RA+CCR7+CD62L+CD95+) were detected with Flow cytometry, further induced TSCM cells expansion in vitro by using IL-2+MEKi+Il-15 combination, TSCM cell-based CAR-T cells were constructed in vitro, further the therapeutic effect of CAR-Tscm cells in MM-loaded NSG mouse model were explored.

Results:

The proportion of TSCM cells is reduced in patients with MM, but their function is stronger than that of CTL cells, and the use of IL-2+ Meki+Il-15 in vitro can induce the expansion of TSCM cells and promote their antitumor capacity; Further, Targeting BCMA CAR-Tscm cells as an effective immune treatment to multiple myeloma patients. CAR-T cells were constructed using TSCM cells in vitro, and in vitro experiments confirmed that they had similar killing effects to conventional CAR-T cells on MM cells in an NSG mouse model of MM tumor burden; CAR-Tscm cells were demonstrated to have similar effects to conventional CAR-T therapy, and demonstrated stronger antitumor effects than conventional CAR-T in contralateral tumorigenic models.

Conclusion:

CAR-Tscm cells are a potentially effective treatment for multiple myeloma.

Disclosures

No relevant conflicts of interest to declare.

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