Bone Marrow Mesenchymal Stromal Cell-mediated Resistance in Multiple Myeloma Against NK Cells can be Overcome by Introduction of CD38-CAR or TRAIL-variant.

ABSTRACT: We have recently shown the strong negative impact of multiple myeloma (MM)-bone marrow mesenchymal stromal cell (BMMSC) interactions to several immunotherapeutic strategies including conventional T cells, chimeric antigen receptor (CAR) T cells, and daratumumab-redirected NK cells. This BMMSC-mediated immune resistance via the upregulation of antiapoptotic proteins in MM cells was mainly observed for moderately cytotoxic modalities. Here, we set out to assess the hypothesis that this distinct mode of immune evasion can be overcome by improving the overall efficacy of immune effector cells. Using an in vitro model, we aimed to improve the cytotoxic potential of KHYG-1 NK cells toward MM cells by the introduction of a CD38-specific CAR and a DR5-specific, optimized TRAIL-variant. Simi

SUBMITTER: Holthof LC 

PROVIDER: S-EPMC8061681 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature