Page 123 - Haematologica Vol. 109 - July 2024
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ARTICLE - Cytotoxic reprogramming for BiTE immunotherapy M. Casey et al.
IL-21 treatment enhances the in vivo efficacy of T-cell- engaging bispecific antibody therapy by modulating cytotoxic T-cell phenotypes in the myeloma bone marrow In order to further understand the impact of rIL-21 treatment on T-cell phenotypes in vivo, we used the Vk14451 myeloma preclinical model.11 Tumor-bearing mice with paraproteinemia were treated with rIL-21, according to a published dosing schedule27 (Figure 5A). Treatment with rIL-21 showed negli-
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gible impacts on tumor burden (Figure 5B) and the number of immune subsets in the myeloma BM (Figure 5C; Online Supplementary Figure S4). However, circulating levels of gran- zyme B, but not IFN-γ, were significantly increased by rIL-21 treatment (Figure 5D). The downregulation of co-receptors CD226 has been recognized as a key feature of dysfunctional T cells in patients with multiple myeloma.30,31 Importantly, rIL-21 treatment significantly increased BM CD8 T cells and
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