Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo

Publication Date:
2018-03-06
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
http://www.aacr.org/
_version_ 1836398818342469632
autor Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
beschreibung Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell–activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy. Experimental Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The chimeric mAbs were tested against human B-cell tumor lines, primary patient samples, and drug-resistant tumors. Results: Chimeric antibodies bound with high affinity to multiple human malignant B-cell lines and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia, including primary tumors from patients who had relapsed after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib-resistant and rituximab-insensitive CD20-deficient variant lymphomas, respectively. Importantly, they demonstrated remarkable in vivo growth inhibition of drug-resistant tumor models in immunodeficient mice. Conclusions: Our method generated novel anti–BAFF-R antibody therapeutics with remarkable single-agent antitumor effects. We propose that these antibodies represent an effective new strategy for targeting and treating drug-resistant B-cell malignancies and warrant further development. Clin Cancer Res; 24(5); 1114–23. ©2017 AACR .
citation_standardnr 6182357
datenlieferant ipn_articles
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feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-03-06
journaleissn 1557-3265
journalissn 1078-0432
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Clinical Cancer Research
relation http://clincancerres.aacrjournals.org/cgi/content/short/24/5/1114?rss=1
search_space articles
shingle_author_1 Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
shingle_author_2 Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
shingle_author_3 Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
shingle_author_4 Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
shingle_catch_all_1 Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell–activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy. Experimental Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The chimeric mAbs were tested against human B-cell tumor lines, primary patient samples, and drug-resistant tumors. Results: Chimeric antibodies bound with high affinity to multiple human malignant B-cell lines and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia, including primary tumors from patients who had relapsed after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib-resistant and rituximab-insensitive CD20-deficient variant lymphomas, respectively. Importantly, they demonstrated remarkable in vivo growth inhibition of drug-resistant tumor models in immunodeficient mice. Conclusions: Our method generated novel anti–BAFF-R antibody therapeutics with remarkable single-agent antitumor effects. We propose that these antibodies represent an effective new strategy for targeting and treating drug-resistant B-cell malignancies and warrant further development. Clin Cancer Res; 24(5); 1114–23. ©2017 AACR .
Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell–activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy. Experimental Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The chimeric mAbs were tested against human B-cell tumor lines, primary patient samples, and drug-resistant tumors. Results: Chimeric antibodies bound with high affinity to multiple human malignant B-cell lines and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia, including primary tumors from patients who had relapsed after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib-resistant and rituximab-insensitive CD20-deficient variant lymphomas, respectively. Importantly, they demonstrated remarkable in vivo growth inhibition of drug-resistant tumor models in immunodeficient mice. Conclusions: Our method generated novel anti–BAFF-R antibody therapeutics with remarkable single-agent antitumor effects. We propose that these antibodies represent an effective new strategy for targeting and treating drug-resistant B-cell malignancies and warrant further development. Clin Cancer Res; 24(5); 1114–23. ©2017 AACR .
Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell–activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy. Experimental Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The chimeric mAbs were tested against human B-cell tumor lines, primary patient samples, and drug-resistant tumors. Results: Chimeric antibodies bound with high affinity to multiple human malignant B-cell lines and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia, including primary tumors from patients who had relapsed after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib-resistant and rituximab-insensitive CD20-deficient variant lymphomas, respectively. Importantly, they demonstrated remarkable in vivo growth inhibition of drug-resistant tumor models in immunodeficient mice. Conclusions: Our method generated novel anti–BAFF-R antibody therapeutics with remarkable single-agent antitumor effects. We propose that these antibodies represent an effective new strategy for targeting and treating drug-resistant B-cell malignancies and warrant further development. Clin Cancer Res; 24(5); 1114–23. ©2017 AACR .
Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell–activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy. Experimental Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The chimeric mAbs were tested against human B-cell tumor lines, primary patient samples, and drug-resistant tumors. Results: Chimeric antibodies bound with high affinity to multiple human malignant B-cell lines and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia, including primary tumors from patients who had relapsed after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib-resistant and rituximab-insensitive CD20-deficient variant lymphomas, respectively. Importantly, they demonstrated remarkable in vivo growth inhibition of drug-resistant tumor models in immunodeficient mice. Conclusions: Our method generated novel anti–BAFF-R antibody therapeutics with remarkable single-agent antitumor effects. We propose that these antibodies represent an effective new strategy for targeting and treating drug-resistant B-cell malignancies and warrant further development. Clin Cancer Res; 24(5); 1114–23. ©2017 AACR .
Qin, H., Wei, G., Sakamaki, I., Dong, Z., Cheng, W. A., Smith, D. L., Wen, F., Sun, H., Kim, K., Cha, S., Bover, L., Neelapu, S. S., Kwak, L. W.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
shingle_title_2 Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
shingle_title_3 Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
shingle_title_4 Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
timestamp 2025-06-30T23:33:06.898Z
titel Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
titel_suche Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo
topic WW-YZ
uid ipn_articles_6182357