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. 2021 Jul 16;9(7):e002475. doi: 10.1136/jitc-2021-002475

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© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.

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CIK cell cytotoxicity is increased by the combination with anti-CD20 mAbs. (A) Violin plots showing 25th and 75th percentiles and median value of the percentage of CD3⁺ CD56⁺ CIK cells and CD16a⁺ CIK cell subsets within day 14 and 21 of cultures generated from healthy donors (n=25). (B) Graphical representation of the CIK+ mAbs combination strategy to target and kill B-cell malignancies (created with BioRender.com). (C) CD20 expression on Raji (Burkitt lymphoma), EHEB (EBV⁺ lymphoma), Karpas-422 (follicular lymphoma), Granta-519 (Mantle cell lymphoma), RCK-8, TMD-8, and OCI-Ly7 (diffuse large B-cell lymphoma) malignant B-cell lines. (D) Cytotoxicity of CIK cells in combination with an irrelevant antibody (CIK +Iso, squares) or with the anti-CD20 mAbs rituximab (CIK +RTX, triangles) or obinutuzumab (CIK +OBI, circles), against the B-cell tumor lines. Lytic activity was measured by a 4-hour calcein-AM release assay performed between days 14 and 21 of CIK cell cultures. The symbols refer to the specific killing of individual CIK cell cultures from different donors at an E/T ratio of 25:1, and mean values±SD (n=6–22) are reported. Data were analyzed by multiple t-test (*p<0.05, **p<0.01, and ****p<0.0001). ADCC, antibody-dependent cell-mediated cytotoxicity; CIK, cytokine induced killer; mAbs, monoclonal antibodies; OBI, obinutuzumab; RTX, rituximab.