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Therapeutic effects of 2B8T2M, a novel fusion of ALT-803, an IL-15 superagonist, with 4 single-chains of anti-CD20 antibody in combination with expanded natural killer cells against rituximab sensitive and resistant Burkitt lymphoma (BL).

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32Background: Patients retreated with rituximab often relapse which limit patient treatment options (Goldman/Cairo, Leukemia, 2013). Our group has successfully expanded functional and active peripheral blood NK cells (exPBNK) to target… Click to show full abstract

32Background: Patients retreated with rituximab often relapse which limit patient treatment options (Goldman/Cairo, Leukemia, 2013). Our group has successfully expanded functional and active peripheral blood NK cells (exPBNK) to target BL (Chu/Cairo, et al, Can Imm Res, 2015). 2B8T2M was generated by fusing ALT-803, an IL-15 superagonist, to four single-chains of rituximab (Liu/Wong, et al, JBC, 2016). 2B8T2M displayed tri-specific CD20 binding activity, activated NK cells to enhance antibody-dependent cellular cytotoxicity, and induced apoptosis of B-lymphoma cells (Liu/Wong, et al, JBC, 2016). Methods: ALT-803 and 2B8T2M were generously provided by Altor BioScience Corporation. NK expansion, NK receptors expression and cytotoxicity were examined as we previous described (Chu/Cairo, et al, Can Imm Res 2015). IFNg and granzyme B levels were examined by ELISA assays. Equal doses of IgG, Rituximab, ALT-803, Rituximab+ALT-803, obinutuzumab (obinu, generously provided by Christian Klein, PhD from Roche) were ...

Keywords: 803 superagonist; single chains; antibody; cd20; alt 803

Journal Title: Journal of Clinical Oncology
Year Published: 2018

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