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Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes

Item Type:Article
Title:Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes
Creators Name:Pfeifer, M. and Zheng, B. and Erdmann, T. and Koeppen, H. and McCord, R. and Grau, M. and Staiger, A. and Chai, A. and Sandmann, T. and Madle, H. and Doerken, B. and Chu, Y.W. and Chen, A.I. and Lebovic, D. and Salles, G.A. and Czuczman, M.S. and Palanca-Wessels, M.C. and Press, O.W. and Advani, R. and Morschhauser, F. and Cheson, B.D. and Lenz, P. and Ott, G. and Polson, A.G. and Mundt, K.E. and Lenz, G.
Abstract:Antibody drug conjugates (ADCs), in which cytotoxic drugs are linked to antibodies targeting antigens on tumor cells, represent promising novel agents for the treatment of malignant lymphomas. Pinatuzumab vedotin is an anti-CD22 ADC and polatuzumab vedotin an anti-CD79B ADC that are both linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In the present study, we analyzed the activity of these agents in different molecular subtypes of diffuse large B-cell lymphoma (DLBCL) both in vitro and in early clinical trials. Both anti-CD22-MMAE and anti-CD79B-MMAE were highly active and induced cell death in the vast majority of activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCL cell lines. Similarly, both agents induced cytotoxicity in models with and without mutations in the signaling molecule CD79B. In line with these observations, relapsed and refractory DLBCL patients of both subtypes responded to these agents. Importantly, a strong correlation between CD22 and CD79B expression in vitro and in vivo was not detectable, indicating that patients should not be excluded from anti-CD22-MMAE or anti-CD79B-MMAE treatment due to low target expression. In summary, these studies suggest that pinatuzumab vedotin and polatuzumab vedotin are active agents for the treatment of patients with different subtypes of DLBCL.
Keywords:Apoptosis, CD79 Antigens, Cell Cycle, Cell Proliferation, Cohort Studies, Cultured Tumor Cells, Diffuse Large B-Cell Lymphoma, Flow Cytometry, Follow-Up Studies, Immunoconjugates, Immunoenzyme Techniques, Monoclonal Antibodies, Mutation, Neoplasm Staging, Phase I as Topic Clinical Trials, Prognosis, Sialic Acid Binding Ig-like Lectin 2, Western Blotting
Publisher:Nature Publishing Group
Page Range:1578-1586
Date:July 2015
Official Publication:https://doi.org/10.1038/leu.2015.48
PubMed:View item in PubMed

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