Page 127 - Haematologica Vol. 109 - July 2024

ARTICLE - Cytotoxic reprogramming for BiTE immunotherapy M. Casey et al. AB
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Figure 7. IL-21 improves effector functions in myeloma bone marrow CD8 T cells stimulated with T-cell-engaging bispecific an- tibody. (A) Primary bone marrow mononuclear cells (BM MNC, 8×105) from 8 patients with newly diagnosed multiple myeloma were stimulated with T-cell-engaging bispecific antibody targeting B-cell maturation antigen (anti-BCMA T-BsAb, 0.2 μg/mL) in the presence or absence of recombinant interleukin-21 (rIL-21, 100 ng/mL) for 3 days. A schematic illustrates the experimental design. (B-D) Representative histograms and box-and-whisker plots showing the expression levels of CD69 (B), CD226 (C), and CD28 (D) on bone marrow (BM) CD8 T cells. Numbers indicate mean fluorescence intensity (MFI). (E) Box and whisker plots showing levels of indicated effector proteins and cytokines in culture supernatants. Data are pooled from 2 experiments (N=8). Differences were tested for statistical significance using a repeated measures ANOVA with a post hoc Holm-Sidak’s multiple comparisons test. *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. TNF-α: tumor necrosis factor-α; GM-CSF: granulocyte-macro- phage colony-stimulating factor.
lesions such as extramedullary disease, though further studies are necessary to understand the impact of IL-21 on the myeloma immune microenvironment.
For clinical translation, rIL-21 treatment has been already tested in combination with rituximab in patients with re- lapsed chronic lymphocytic leukemia and low-grade B-cell
lymphomas, and that weekly injection of rIL-21 (100 μg/kg) was tolerable in patients.48 Besides, a recent preclinical study has also shown no major immune-mediated toxicities either alone or in combination with immune checkpoint inhibi- tors.27 One of the limitations of our study is that we could not address whether or not the addition of rIL-21 has an
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