Journal Article

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

Chai, A, Ott, G, Lebovic, D, Chu, Y-W, Morschhauser, F, Sandmann, T, Grau, M, Polson, A G, Dörken, B, Chen, A I, McCord, R, Press, O W, Koeppen, H, Palanca-Wessels, M C, Advani, R, Czuczman, M S, Pfeifer, M, Lenz, P, Zheng, B, Madle, H, Lenz, G, Mundt, K E, Staiger, A, Cheson, B D, Erdmann, T, Salles, G A

2015

Overview

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 because of 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/2 / 13/21 / 13/31 / 13/51 / 631/250/249/1623 / 692/308/2779/109 / 692/699/67/1059/602 / 692/699/67/1990/291/1621/1915 / 692/700/565/251 / Antibodies / Antibodies, Monoclonal - pharmacology / Antigen (tumor-associated) / Antigens / Apoptosis - drug effects / B-cell lymphoma / Biocompatibility / Blotting, Western / Cancer Research / Care and treatment / CD22 antigen / CD79 Antigens - genetics / CD79 Antigens - immunology / Cell Cycle - drug effects / Cell death / Cell Proliferation - drug effects / Clinical trials / Clinical Trials, Phase I as Topic / Cohort Studies / Conjugates / Critical Care Medicine / Cytotoxicity / Disruption / Flow Cytometry / Follow-Up Studies / Genetic aspects / Hematology / Humans / Immunoconjugates - pharmacology / Immunoenzyme Techniques / Immunotherapy / Intensive / Internal Medicine / Lymphocytes B / Lymphoma / Lymphoma, Large B-Cell, Diffuse - classification / Lymphoma, Large B-Cell, Diffuse - drug therapy / Lymphoma, Large B-Cell, Diffuse - immunology / Lymphoma, Large B-Cell, Diffuse - pathology / Lymphomas / Medicine / Medicine & Public Health / Methods / Monoclonal antibodies / Mutation / Mutation - genetics / Neoplasm Staging / Oncology / original-article / Patient outcomes / Patients / Prognosis / Sialic Acid Binding Ig-like Lectin 2 - genetics / Sialic Acid Binding Ig-like Lectin 2 - immunology / Toxicity / Tumor cells / Tumor Cells, Cultured