Data from AGS67E, an Anti-CD37 Monomethyl Auristatin E Antibody–Drug Conjugate as a Potential Therapeutic for B/T-Cell Malignancies and AML: A New Role for CD37 in AML Article Swipe

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Daniel S. Pereira , Claudia Guevara , Liqing Jin , Nathan Mbong , Alla Verlinsky , Ssucheng J. Hsu , Héctor Aviña , Sher Karki , Joseph D. Abad , Peng Yang , Sungju Moon , Faisal Malik , Michael Y. Choi , Zili An , Kendall Morrison , Pia M. Challita-Eid , Fernando Doñate , Ingrid B.J. Joseph , Thomas J. Kipps , John E. Dick , David R. Stover ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1158/1535-7163.c.6536874

CD37 is a tetraspanin expressed on malignant B cells. Recently, CD37 has gained interest as a therapeutic target. We developed AGS67E, an antibody–drug conjugate that targets CD37 for the potential treatment of B/T-cell malignancies. It is a fully human monoclonal IgG2 antibody (AGS67C) conjugated, via a protease-cleavable linker, to the microtubule-disrupting agent monomethyl auristatin E (MMAE). AGS67E induces potent cytotoxicity, apoptosis, and cell-cycle alterations in many non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) cell lines and patient-derived samples in vitro. It also shows potent antitumor activity in NHL and CLL xenografts, including Rituxan-refractory models. During profiling studies to confirm the reported expression of CD37 in normal tissues and B-cell malignancies, we made the novel discovery that the CD37 protein was expressed in T-cell lymphomas and in AML. AGS67E bound to >80% of NHL and T-cell lymphomas, 100% of CLL and 100% of AML patient-derived samples, including CD34⁺CD38⁻ leukemic stem cells. It also induced cytotoxicity, apoptosis, and cell-cycle alterations in AML cell lines and antitumor efficacy in orthotopic AML xenografts. Taken together, this study shows not only that AGS67E may serve as a potential therapeutic for B/T-cell malignancies, but it also demonstrates, for the first time, that CD37 is well expressed and a potential drug target in AML. Mol Cancer Ther; 14(7); 1650–60. ©2015 AACR.

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Antibody-drug conjugate Medicine Conjugate Drug Pharmacology Antibody Cancer research Oncology Monoclonal antibody Immunology Mathematical analysis Mathematics

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/1535-7163.c.6536874
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Title: Data from AGS67E, an Anti-CD37 Monomethyl Auristatin E Antibody–Drug Conjugate as a Potential Therapeutic for B/T-Cell Malignancies and AML: A New Role for CD37 in AML

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Publication year: 2023

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Publication date: 2023-04-03

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Authors: Daniel S. Pereira, Claudia Guevara, Liqing Jin, Nathan Mbong, Alla Verlinsky, Ssucheng J. Hsu, Héctor Aviña, Sher Karki, Joseph D. Abad, Peng Yang, Sungju Moon, Faisal Malik, Michael Y. Choi, Zili An, Kendall Morrison, Pia M. Challita-Eid, Fernando Doñate, Ingrid B.J. Joseph, Thomas J. Kipps, John E. Dick, David R. Stover

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Concepts: Antibody-drug conjugate, Medicine, Conjugate, Drug, Pharmacology, Antibody, Cancer research, Oncology, Monoclonal antibody, Immunology, Mathematical analysis, Mathematics

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abstract_inverted_index.potential	29, 183, 203
abstract_inverted_index.profiling	96
abstract_inverted_index.together,	171
abstract_inverted_index.treatment	30
abstract_inverted_index.1650–60.	212
abstract_inverted_index.apoptosis,	60, 155
abstract_inverted_index.auristatin	53
abstract_inverted_index.cell-cycle	62, 157
abstract_inverted_index.expression	102
abstract_inverted_index.lymphomas,	136
abstract_inverted_index.monoclonal	39
abstract_inverted_index.monomethyl	52
abstract_inverted_index.orthotopic	167
abstract_inverted_index.<i>in	79
abstract_inverted_index.alterations	63, 158
abstract_inverted_index.conjugated,	43
abstract_inverted_index.lymphocytic	71
abstract_inverted_index.non-Hodgkin	66
abstract_inverted_index.tetraspanin	3
abstract_inverted_index.therapeutic	16, 184
abstract_inverted_index.xenografts,	91
abstract_inverted_index.xenografts.	169
abstract_inverted_index.<i>Mol	208
abstract_inverted_index.cytotoxicity,	59, 154
abstract_inverted_index.demonstrates,	191
abstract_inverted_index.malignancies,	110, 187
abstract_inverted_index.malignancies.	33
abstract_inverted_index.antibody–drug	22
abstract_inverted_index.patient-derived	77, 144
abstract_inverted_index.vitro</i>.	80
abstract_inverted_index.Rituxan-refractory	93
abstract_inverted_index.protease-cleavable	46
abstract_inverted_index.microtubule-disrupting	50
abstract_inverted_index.<div>Abstract<p>CD37	0
abstract_inverted_index.AACR</i>.</p></div>	214
abstract_inverted_index.CD34<sup>+</sup>CD38<sup>−</sup>	147
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	21
sustainable_development_goals[0].id	https://metadata.un.org/sdg/3
sustainable_development_goals[0].score	0.6899999976158142
sustainable_development_goals[0].display_name	Good health and well-being
citation_normalized_percentile.value	0.55785889
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False