High-throughput optofluidic screening of single B cells identifies novel cross-reactive antibodies as inhibitors of uPAR with antibody-dependent effector functions

The urokinase-type plasminogen activator receptor (uPAR) is an essential regulator for cell signaling in tumor cell proliferation, adhesion, and metastasis. The ubiquitous nature of uPAR in many aggressive cancer types makes uPAR an attractive target for immunotherapy. Here, we present a rapid and s...

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Published in:	mAbs Vol. 15; no. 1; p. 2184197
Main Authors:	Lourenço, André Luiz, Chuo, Shih-Wei, Bohn, Markus F, Hann, Byron, Khan, Shireen, Yevalekar, Neha, Patel, Nitin, Yang, Teddy, Xu, Lina, Lv, Dandan, Drakas, Robert, Lively, Sarah, Craik, Charles S
Format:	Journal Article
Language:	English
Published:	United States Taylor & Francis 2023 Taylor & Francis Group
Subjects:	Animals Antibodies Antibody-dependent cellular cytotoxicity (ADCC) B-Lymphocytes cancer therapeutics cross-reactive antibody Humans Leukocytes, Mononuclear Mice Receptors, Urokinase Plasminogen Activator Signal Transduction single B-cell screening Urokinase-type plasminogen activator receptor (uPAR) cross-reactive antibody cancer therapeutics Urokinase-type plasminogen activator receptor (uPAR) single B-cell screening Antibody-dependent cellular cytotoxicity (ADCC)
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Abstract	The urokinase-type plasminogen activator receptor (uPAR) is an essential regulator for cell signaling in tumor cell proliferation, adhesion, and metastasis. The ubiquitous nature of uPAR in many aggressive cancer types makes uPAR an attractive target for immunotherapy. Here, we present a rapid and successful workflow for developing cross-reactive anti-uPAR recombinant antibodies (rAbs) using high-throughput optofluidic screening of single B-cells from human uPAR-immunized mice. A total of 80 human and cynomolgus uPAR cross-reactive plasma cells were identified, and selected mouse VH/VL domains were linked to the trastuzumab (Herceptin®) constant domains for the expression of mouse-human chimeric antibodies. The resulting rAbs were characterized by their tumor-cell recognition, binding activity, and cell adhesion inhibition on triple-negative breast cancer cells. In addition, the rAbs were shown to enact antibody-dependent cellular cytotoxicity (ADCC) in the presence of either human natural killer cells or peripheral blood mononuclear cells, and were evaluated for the potential use of uPAR-targeting antibody-drug conjugates (ADCs). Three lead antibodies (11857, 8163, and 3159) were evaluated for their therapeutic efficacy and were shown to suppress tumor growth. Finally, the binding epitopes of the lead antibodies were characterized, providing information on their unique binding modes to uPAR. Altogether, the strategy identified unique cross-reactive antibodies with ADCC, ADC, and functional inhibitory effects by targeting cell-surface uPAR, that can be tested in safety studies and serve as potential immunotherapeutics.
AbstractList	ABSTRACTThe urokinase-type plasminogen activator receptor (uPAR) is an essential regulator for cell signaling in tumor cell proliferation, adhesion, and metastasis. The ubiquitous nature of uPAR in many aggressive cancer types makes uPAR an attractive target for immunotherapy. Here, we present a rapid and successful workflow for developing cross-reactive anti-uPAR recombinant antibodies (rAbs) using high-throughput optofluidic screening of single B-cells from human uPAR-immunized mice. A total of 80 human and cynomolgus uPAR cross-reactive plasma cells were identified, and selected mouse VH/VL domains were linked to the trastuzumab (Herceptin®) constant domains for the expression of mouse-human chimeric antibodies. The resulting rAbs were characterized by their tumor-cell recognition, binding activity, and cell adhesion inhibition on triple-negative breast cancer cells. In addition, the rAbs were shown to enact antibody-dependent cellular cytotoxicity (ADCC) in the presence of either human natural killer cells or peripheral blood mononuclear cells, and were evaluated for the potential use of uPAR-targeting antibody-drug conjugates (ADCs). Three lead antibodies (11857, 8163, and 3159) were evaluated for their therapeutic efficacy in vivo and were shown to suppress tumor growth. Finally, the binding epitopes of the lead antibodies were characterized, providing information on their unique binding modes to uPAR. Altogether, the strategy identified unique cross-reactive antibodies with ADCC, ADC, and functional inhibitory effects by targeting cell-surface uPAR, that can be tested in safety studies and serve as potential immunotherapeutics. The urokinase-type plasminogen activator receptor (uPAR) is an essential regulator for cell signaling in tumor cell proliferation, adhesion, and metastasis. The ubiquitous nature of uPAR in many aggressive cancer types makes uPAR an attractive target for immunotherapy. Here, we present a rapid and successful workflow for developing cross-reactive anti-uPAR recombinant antibodies (rAbs) using high-throughput optofluidic screening of single B-cells from human uPAR-immunized mice. A total of 80 human and cynomolgus uPAR cross-reactive plasma cells were identified, and selected mouse VH/VL domains were linked to the trastuzumab (Herceptin®) constant domains for the expression of mouse-human chimeric antibodies. The resulting rAbs were characterized by their tumor-cell recognition, binding activity, and cell adhesion inhibition on triple-negative breast cancer cells. In addition, the rAbs were shown to enact antibody-dependent cellular cytotoxicity (ADCC) in the presence of either human natural killer cells or peripheral blood mononuclear cells, and were evaluated for the potential use of uPAR-targeting antibody-drug conjugates (ADCs). Three lead antibodies (11857, 8163, and 3159) were evaluated for their therapeutic efficacy in vivo and were shown to suppress tumor growth. Finally, the binding epitopes of the lead antibodies were characterized, providing information on their unique binding modes to uPAR. Altogether, the strategy identified unique cross-reactive antibodies with ADCC, ADC, and functional inhibitory effects by targeting cell-surface uPAR, that can be tested in safety studies and serve as potential immunotherapeutics. The urokinase-type plasminogen activator receptor (uPAR) is an essential regulator for cell signaling in tumor cell proliferation, adhesion, and metastasis. The ubiquitous nature of uPAR in many aggressive cancer types makes uPAR an attractive target for immunotherapy. Here, we present a rapid and successful workflow for developing cross-reactive anti-uPAR recombinant antibodies (rAbs) using high-throughput optofluidic screening of single B-cells from human uPAR-immunized mice. A total of 80 human and cynomolgus uPAR cross-reactive plasma cells were identified, and selected mouse VH/VL domains were linked to the trastuzumab (Herceptin®) constant domains for the expression of mouse-human chimeric antibodies. The resulting rAbs were characterized by their tumor-cell recognition, binding activity, and cell adhesion inhibition on triple-negative breast cancer cells. In addition, the rAbs were shown to enact antibody-dependent cellular cytotoxicity (ADCC) in the presence of either human natural killer cells or peripheral blood mononuclear cells, and were evaluated for the potential use of uPAR-targeting antibody-drug conjugates (ADCs). Three lead antibodies (11857, 8163, and 3159) were evaluated for their therapeutic efficacy and were shown to suppress tumor growth. Finally, the binding epitopes of the lead antibodies were characterized, providing information on their unique binding modes to uPAR. Altogether, the strategy identified unique cross-reactive antibodies with ADCC, ADC, and functional inhibitory effects by targeting cell-surface uPAR, that can be tested in safety studies and serve as potential immunotherapeutics.
Author	Yang, Teddy Chuo, Shih-Wei Bohn, Markus F Drakas, Robert Yevalekar, Neha Khan, Shireen Lv, Dandan Hann, Byron Lourenço, André Luiz Patel, Nitin Xu, Lina Lively, Sarah Craik, Charles S
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Keywords	cross-reactive antibody cancer therapeutics Urokinase-type plasminogen activator receptor (uPAR) single B-cell screening Antibody-dependent cellular cytotoxicity (ADCC)
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References	Konecny G (e_1_3_6_11_1) 2001; 7 e_1_3_6_30_1 e_1_3_6_53_1 e_1_3_6_32_1 e_1_3_6_55_1 e_1_3_6_72_1 e_1_3_6_51_1 e_1_3_6_70_1 e_1_3_6_15_1 e_1_3_6_38_1 e_1_3_6_13_1 e_1_3_6_19_1 e_1_3_6_34_1 e_1_3_6_57_1 e_1_3_6_17_1 e_1_3_6_36_1 e_1_3_6_59_1 e_1_3_6_42_1 e_1_3_6_65_1 e_1_3_6_21_1 e_1_3_6_44_1 e_1_3_6_63_1 e_1_3_6_2_1 e_1_3_6_61_1 e_1_3_6_40_1 e_1_3_6_6_1 e_1_3_6_4_1 e_1_3_6_8_1 e_1_3_6_27_1 e_1_3_6_29_1 e_1_3_6_23_1 e_1_3_6_46_1 e_1_3_6_69_1 e_1_3_6_25_1 e_1_3_6_48_1 e_1_3_6_67_1 e_1_3_6_31_1 e_1_3_6_52_1 e_1_3_6_33_1 e_1_3_6_54_1 e_1_3_6_10_1 e_1_3_6_73_1 e_1_3_6_50_1 e_1_3_6_71_1 e_1_3_6_14_1 e_1_3_6_39_1 e_1_3_6_12_1 e_1_3_6_18_1 e_1_3_6_35_1 e_1_3_6_56_1 e_1_3_6_16_1 e_1_3_6_37_1 e_1_3_6_58_1 e_1_3_6_20_1 e_1_3_6_41_1 e_1_3_6_66_1 e_1_3_6_22_1 e_1_3_6_43_1 e_1_3_6_64_1 e_1_3_6_62_1 e_1_3_6_60_1 e_1_3_6_5_1 e_1_3_6_3_1 e_1_3_6_9_1 e_1_3_6_7_1 e_1_3_6_28_1 e_1_3_6_49_1 e_1_3_6_24_1 e_1_3_6_45_1 e_1_3_6_26_1 e_1_3_6_47_1 e_1_3_6_68_1
References_xml	– ident: e_1_3_6_5_1 doi: 10.3390/diagnostics10110877 – ident: e_1_3_6_17_1 doi: 10.1158/1078-0432.CCR-09-0636 – ident: e_1_3_6_68_1 doi: 10.1016/S0021-9258(18)61211-6 – ident: e_1_3_6_31_1 doi: 10.1016/j.it.2021.10.008 – ident: e_1_3_6_9_1 doi: 10.1158/0008-5472.CAN-03-3848 – ident: e_1_3_6_13_1 doi: 10.18632/oncoscience.146 – ident: e_1_3_6_25_1 doi: 10.3390/antib8040054 – ident: e_1_3_6_54_1 doi: 10.1016/j.jbc.2021.100826 – ident: e_1_3_6_2_1 doi: 10.1038/nrm2821 – ident: e_1_3_6_70_1 doi: 10.1038/nsmb.1404 – ident: e_1_3_6_37_1 doi: 10.2165/00003495-200262010-00008 – ident: e_1_3_6_58_1 doi: 10.2217/imt.12.38 – ident: e_1_3_6_6_1 doi: 10.7754/Clin.Lab.2017.170110 – ident: e_1_3_6_22_1 doi: 10.1016/j.bmc.2012.12.047 – ident: e_1_3_6_29_1 doi: 10.1016/j.dmpk.2018.02.003 – ident: e_1_3_6_36_1 doi: 10.1371/journal.pone.0121673 – ident: e_1_3_6_32_1 doi: 10.1007/978-1-59745-248-9_8 – ident: e_1_3_6_39_1 doi: 10.1158/2326-6066.CIR-15-0059 – ident: e_1_3_6_49_1 doi: 10.1038/s41591-020-0998-x – ident: e_1_3_6_55_1 doi: 10.1128/JVI.02194-14 – ident: e_1_3_6_46_1 doi: 10.1038/s41413-020-0094-3 – ident: e_1_3_6_35_1 doi: 10.1186/1479-5876-11-307 – ident: e_1_3_6_15_1 doi: 10.1002/ijc.25159 – ident: e_1_3_6_43_1 doi: 10.7150/thno.7323 – ident: e_1_3_6_56_1 doi: 10.3390/v11010069 – ident: e_1_3_6_67_1 doi: 10.7150/thno.4218 – ident: e_1_3_6_66_1 doi: 10.1371/journal.pone.0003730 – ident: e_1_3_6_19_1 doi: 10.1016/j.jmb.2015.01.022 – volume: 7 start-page: 2448 issue: 8 year: 2001 ident: e_1_3_6_11_1 article-title: Her-2/neu and urokinase-type plasminogen activator and its inhibitor in breast cancer publication-title: Clin Cancer Res contributor: fullname: Konecny G – ident: e_1_3_6_14_1 doi: 10.1159/000151738 – ident: e_1_3_6_48_1 doi: 10.1016/j.imlet.2018.02.006 – ident: e_1_3_6_21_1 doi: 10.1002/ange.201510866 – ident: e_1_3_6_44_1 doi: 10.1074/jbc.M610184200 – ident: e_1_3_6_8_1 doi: 10.1016/j.drudis.2021.01.016 – ident: e_1_3_6_73_1 doi: 10.1093/molbev/msy096 – ident: e_1_3_6_42_1 doi: 10.15252/embj.201387611 – ident: e_1_3_6_24_1 doi: 10.1158/1078-0432.CCR-10-2258 – ident: e_1_3_6_33_1 doi: 10.1038/sj.bjc.6602930 – ident: e_1_3_6_64_1 doi: 10.1186/s13058-021-01459-y – ident: e_1_3_6_52_1 doi: 10.1038/s41598-019-48323-w – ident: e_1_3_6_72_1 doi: 10.1093/nar/gkac240 – ident: e_1_3_6_53_1 doi: 10.1016/j.ab.2021.114411 – ident: e_1_3_6_38_1 doi: 10.3390/jcm8020254 – ident: e_1_3_6_69_1 doi: 10.1016/S0021-9258(19)85069-X – ident: e_1_3_6_71_1 doi: 10.1002/eji.201746944 – ident: e_1_3_6_26_1 doi: 10.2174/138945011797635812 – ident: e_1_3_6_60_1 doi: 10.1016/S0021-9258(18)31646-6 – ident: e_1_3_6_59_1 doi: 10.1182/blood-2012-08-451187 – ident: e_1_3_6_62_1 doi: 10.1002/jcp.1133 – ident: e_1_3_6_28_1 doi: 10.1074/jbc.M109.077677 – ident: e_1_3_6_10_1 doi: 10.1038/nrclinonc.2016.66 – ident: e_1_3_6_16_1 doi: 10.1586/era.10.226 – ident: e_1_3_6_51_1 doi: 10.3390/cancers13081988 – ident: e_1_3_6_12_1 doi: 10.1074/jbc.M109.023960 – ident: e_1_3_6_63_1 doi: 10.1083/jcb.200612058 – ident: e_1_3_6_40_1 doi: 10.1080/19420862.2021.1951427 – ident: e_1_3_6_30_1 doi: 10.1080/19420862.2019.1624126 – ident: e_1_3_6_7_1 doi: 10.1002/med.10054 – ident: e_1_3_6_50_1 doi: 10.3390/cancers13020312 – ident: e_1_3_6_65_1 doi: 10.1091/mbc.10.1.179 – ident: e_1_3_6_23_1 doi: 10.1038/s41598-019-47900-3 – ident: e_1_3_6_4_1 doi: 10.2174/138161211796718152 – ident: e_1_3_6_20_1 doi: 10.1593/neo.10296 – ident: e_1_3_6_61_1 doi: 10.1083/jcb.134.6.1563 – ident: e_1_3_6_3_1 doi: 10.2174/138945011797635902 – ident: e_1_3_6_27_1 doi: 10.1186/s13550-020-00673-7 – ident: e_1_3_6_47_1 doi: 10.1124/dmd.114.062679 – ident: e_1_3_6_34_1 doi: 10.1038/s12276-019-0345-9 – ident: e_1_3_6_18_1 doi: 10.1158/0008-5472.CAN-12-3526 – ident: e_1_3_6_57_1 doi: 10.3389/fimmu.2019.02875 – ident: e_1_3_6_41_1 doi: 10.1016/j.ccell.2022.07.005 – ident: e_1_3_6_45_1 doi: 10.3389/fonc.2018.00024
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Snippet	The urokinase-type plasminogen activator receptor (uPAR) is an essential regulator for cell signaling in tumor cell proliferation, adhesion, and metastasis.... ABSTRACTThe urokinase-type plasminogen activator receptor (uPAR) is an essential regulator for cell signaling in tumor cell proliferation, adhesion, and...
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SubjectTerms	Animals Antibodies Antibody-dependent cellular cytotoxicity (ADCC) B-Lymphocytes cancer therapeutics cross-reactive antibody Humans Leukocytes, Mononuclear Mice Receptors, Urokinase Plasminogen Activator Signal Transduction single B-cell screening Urokinase-type plasminogen activator receptor (uPAR)
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Title	High-throughput optofluidic screening of single B cells identifies novel cross-reactive antibodies as inhibitors of uPAR with antibody-dependent effector functions
URI	https://www.ncbi.nlm.nih.gov/pubmed/36859773 https://search.proquest.com/docview/2781624697 https://pubmed.ncbi.nlm.nih.gov/PMC9988344 https://doaj.org/article/069d547a08b64d7f92e26a8d69854d53
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