Eintrag weiter verarbeiten
Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats.
Gespeichert in:
| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , |
| In: | Blood, 110, 2007, 11, S. 2361-2361 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
|
| Schlagwörter: |
| author_facet |
Xie, Dong Deng, Rong Baudys, Jakub Chan, Pam Dere, Randy Ebens, Allen Fielder, Paul Fuji, Reina Gray, Alane Hung, Catherine Iyer, Suhas McKeever, Kathleen Kenrick, Margaret Leach, Will Polson, Andrew Saad, Ola Stephan, Jean-Philippe Shen, Ben Quan Tibbitts, Jay Yu, Shang-Fan Prabhu, Saileta Xie, Dong Deng, Rong Baudys, Jakub Chan, Pam Dere, Randy Ebens, Allen Fielder, Paul Fuji, Reina Gray, Alane Hung, Catherine Iyer, Suhas McKeever, Kathleen Kenrick, Margaret Leach, Will Polson, Andrew Saad, Ola Stephan, Jean-Philippe Shen, Ben Quan Tibbitts, Jay Yu, Shang-Fan Prabhu, Saileta |
|---|---|
| author |
Xie, Dong Deng, Rong Baudys, Jakub Chan, Pam Dere, Randy Ebens, Allen Fielder, Paul Fuji, Reina Gray, Alane Hung, Catherine Iyer, Suhas McKeever, Kathleen Kenrick, Margaret Leach, Will Polson, Andrew Saad, Ola Stephan, Jean-Philippe Shen, Ben Quan Tibbitts, Jay Yu, Shang-Fan Prabhu, Saileta |
| spellingShingle |
Xie, Dong Deng, Rong Baudys, Jakub Chan, Pam Dere, Randy Ebens, Allen Fielder, Paul Fuji, Reina Gray, Alane Hung, Catherine Iyer, Suhas McKeever, Kathleen Kenrick, Margaret Leach, Will Polson, Andrew Saad, Ola Stephan, Jean-Philippe Shen, Ben Quan Tibbitts, Jay Yu, Shang-Fan Prabhu, Saileta Blood Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. Cell Biology Hematology Immunology Biochemistry |
| author_sort |
xie, dong |
| spelling |
Xie, Dong Deng, Rong Baudys, Jakub Chan, Pam Dere, Randy Ebens, Allen Fielder, Paul Fuji, Reina Gray, Alane Hung, Catherine Iyer, Suhas McKeever, Kathleen Kenrick, Margaret Leach, Will Polson, Andrew Saad, Ola Stephan, Jean-Philippe Shen, Ben Quan Tibbitts, Jay Yu, Shang-Fan Prabhu, Saileta 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v110.11.2361.2361 <jats:title>Abstract</jats:title> <jats:p>CD22 is a B cell specific antigen and is expressed in Non-Hodgkin lymphoma (NHL) with limited expression on normal tissues. Currently, we are evaluating anti-CD22 antibody drug conjugates (anti-CD22 ADC) consisting of a humanized monoclonal IgG antibody conjugated to mitotic inhibitors such as DM1 (a maytansinoid), Monomethylauristatin F (MMAF), or Monomethylauristatin E (MMAE). The antibody binds to human and cynomolgus monkey CD22, but does not bind to rodent CD22. The cytotoxic drugs were conjugated to the antibody via uncleavable linkers (MCC-DM1, MC-MMAF) or cleavable linkers (SPP-DM1, vc-MMAE). These conjugates have demonstrated anti-tumor activity in mouse xenograft models of human B-cell tumors. This study was to assess and to compare the antigen-independent pharmacokinetics of anti-CD22 ADCs with uncleavable linkers (anti-CD22-MCC-DM1 and anti-CD22-MC-MMAF) and cleavable linkers (anti-CD22-SPP-DM1 and anti-CD22-vc-MMAE) in rats, and to support a pilot rat safety study. Following a single IV dose, the anti-CD22 ADCs exhibited a biphasic disposition profile. The conjugates with cleavable linkers had faster clearance compared to those with uncleavable linkers (59.4 mL/day/kg for anti-CD22-SPP-DM1 vs. 18.0 mL/day/kg for anti-CD22-MCC-DM1). The faster clearance for anti-CD22 ADCs with cleavable linker has also been observed with other ADCs (different target). In addition, it was found that free DM1 in plasma that was deconjugated from anti-CD22-SPP-DM1 had ∼70 fold higher exposure compared with that from anti-CD22-MCC-DM1 (area under curve (AUC) for free DM1 in plasma: 562 day*ng/mL for anti-CD22-SPP-DM1 vs. 8.18 day*ng/mL for anti-CD22-MCC-DM1). Furthermore, anti-CD22-SPP-DM1 had a different DM1 release profile compared with anti-CD22-MCC-DM1 when incubated with human plasma in vitro. Maximum concentrations of free DM1 were reached at ∼6 hr and ∼24 hr for anti-CD22-SPP-DM1 and anti-CD22-MCC-DM1, respectively. These observations were consistent with the safety findings in rats: anti-CD22-SPP-DM1 had greater toxicity (body weight loss, renal toxicity) compared with anti-CD22-MCC-DM1. The data described here indicate that the anti-CD22 ADCs with uncleavable linkers are cleared slower than, and have a better safety profile than the conjugates with cleavable linkers.</jats:p> Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. Blood |
| doi_str_mv |
10.1182/blood.v110.11.2361.2361 |
| facet_avail |
Online Free |
| finc_class_facet |
Biologie Medizin Chemie und Pharmazie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52MTEwLjExLjIzNjEuMjM2MQ |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52MTEwLjExLjIzNjEuMjM2MQ |
| institution |
DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-D161 DE-Zwi2 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 |
| imprint |
American Society of Hematology, 2007 |
| imprint_str_mv |
American Society of Hematology, 2007 |
| issn |
0006-4971 1528-0020 |
| issn_str_mv |
0006-4971 1528-0020 |
| language |
English |
| mega_collection |
American Society of Hematology (CrossRef) |
| match_str |
xie2007pharmacokineticsofanticd22antibodyconjugateswithuncleavableandcleavablelinkersinrats |
| publishDateSort |
2007 |
| publisher |
American Society of Hematology |
| recordtype |
ai |
| record_format |
ai |
| series |
Blood |
| source_id |
49 |
| title |
Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_unstemmed |
Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_full |
Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_fullStr |
Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_full_unstemmed |
Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_short |
Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_sort |
pharmacokinetics of anti-cd22 antibody conjugates with uncleavable and cleavable linkers in rats. |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood.v110.11.2361.2361 |
| publishDate |
2007 |
| physical |
2361-2361 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>CD22 is a B cell specific antigen and is expressed in Non-Hodgkin lymphoma (NHL) with limited expression on normal tissues. Currently, we are evaluating anti-CD22 antibody drug conjugates (anti-CD22 ADC) consisting of a humanized monoclonal IgG antibody conjugated to mitotic inhibitors such as DM1 (a maytansinoid), Monomethylauristatin F (MMAF), or Monomethylauristatin E (MMAE). The antibody binds to human and cynomolgus monkey CD22, but does not bind to rodent CD22. The cytotoxic drugs were conjugated to the antibody via uncleavable linkers (MCC-DM1, MC-MMAF) or cleavable linkers (SPP-DM1, vc-MMAE). These conjugates have demonstrated anti-tumor activity in mouse xenograft models of human B-cell tumors. This study was to assess and to compare the antigen-independent pharmacokinetics of anti-CD22 ADCs with uncleavable linkers (anti-CD22-MCC-DM1 and anti-CD22-MC-MMAF) and cleavable linkers (anti-CD22-SPP-DM1 and anti-CD22-vc-MMAE) in rats, and to support a pilot rat safety study. Following a single IV dose, the anti-CD22 ADCs exhibited a biphasic disposition profile. The conjugates with cleavable linkers had faster clearance compared to those with uncleavable linkers (59.4 mL/day/kg for anti-CD22-SPP-DM1 vs. 18.0 mL/day/kg for anti-CD22-MCC-DM1). The faster clearance for anti-CD22 ADCs with cleavable linker has also been observed with other ADCs (different target). In addition, it was found that free DM1 in plasma that was deconjugated from anti-CD22-SPP-DM1 had ∼70 fold higher exposure compared with that from anti-CD22-MCC-DM1 (area under curve (AUC) for free DM1 in plasma: 562 day*ng/mL for anti-CD22-SPP-DM1 vs. 8.18 day*ng/mL for anti-CD22-MCC-DM1). Furthermore, anti-CD22-SPP-DM1 had a different DM1 release profile compared with anti-CD22-MCC-DM1 when incubated with human plasma in vitro. Maximum concentrations of free DM1 were reached at ∼6 hr and ∼24 hr for anti-CD22-SPP-DM1 and anti-CD22-MCC-DM1, respectively. These observations were consistent with the safety findings in rats: anti-CD22-SPP-DM1 had greater toxicity (body weight loss, renal toxicity) compared with anti-CD22-MCC-DM1. The data described here indicate that the anti-CD22 ADCs with uncleavable linkers are cleared slower than, and have a better safety profile than the conjugates with cleavable linkers.</jats:p> |
| container_issue |
11 |
| container_start_page |
2361 |
| container_title |
Blood |
| container_volume |
110 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792322358842753024 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T11:16:37.632Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Pharmacokinetics+of+Anti-CD22+Antibody+Conjugates+with+Uncleavable+and+Cleavable+Linkers+in+Rats.&rft.date=2007-11-16&genre=article&issn=1528-0020&volume=110&issue=11&spage=2361&epage=2361&pages=2361-2361&jtitle=Blood&atitle=Pharmacokinetics+of+Anti-CD22+Antibody+Conjugates+with+Uncleavable+and+Cleavable+Linkers+in+Rats.&aulast=Prabhu&aufirst=Saileta&rft_id=info%3Adoi%2F10.1182%2Fblood.v110.11.2361.2361&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792322358842753024 |
| author | Xie, Dong, Deng, Rong, Baudys, Jakub, Chan, Pam, Dere, Randy, Ebens, Allen, Fielder, Paul, Fuji, Reina, Gray, Alane, Hung, Catherine, Iyer, Suhas, McKeever, Kathleen, Kenrick, Margaret, Leach, Will, Polson, Andrew, Saad, Ola, Stephan, Jean-Philippe, Shen, Ben Quan, Tibbitts, Jay, Yu, Shang-Fan, Prabhu, Saileta |
| author_facet | Xie, Dong, Deng, Rong, Baudys, Jakub, Chan, Pam, Dere, Randy, Ebens, Allen, Fielder, Paul, Fuji, Reina, Gray, Alane, Hung, Catherine, Iyer, Suhas, McKeever, Kathleen, Kenrick, Margaret, Leach, Will, Polson, Andrew, Saad, Ola, Stephan, Jean-Philippe, Shen, Ben Quan, Tibbitts, Jay, Yu, Shang-Fan, Prabhu, Saileta, Xie, Dong, Deng, Rong, Baudys, Jakub, Chan, Pam, Dere, Randy, Ebens, Allen, Fielder, Paul, Fuji, Reina, Gray, Alane, Hung, Catherine, Iyer, Suhas, McKeever, Kathleen, Kenrick, Margaret, Leach, Will, Polson, Andrew, Saad, Ola, Stephan, Jean-Philippe, Shen, Ben Quan, Tibbitts, Jay, Yu, Shang-Fan, Prabhu, Saileta |
| author_sort | xie, dong |
| container_issue | 11 |
| container_start_page | 2361 |
| container_title | Blood |
| container_volume | 110 |
| description | <jats:title>Abstract</jats:title> <jats:p>CD22 is a B cell specific antigen and is expressed in Non-Hodgkin lymphoma (NHL) with limited expression on normal tissues. Currently, we are evaluating anti-CD22 antibody drug conjugates (anti-CD22 ADC) consisting of a humanized monoclonal IgG antibody conjugated to mitotic inhibitors such as DM1 (a maytansinoid), Monomethylauristatin F (MMAF), or Monomethylauristatin E (MMAE). The antibody binds to human and cynomolgus monkey CD22, but does not bind to rodent CD22. The cytotoxic drugs were conjugated to the antibody via uncleavable linkers (MCC-DM1, MC-MMAF) or cleavable linkers (SPP-DM1, vc-MMAE). These conjugates have demonstrated anti-tumor activity in mouse xenograft models of human B-cell tumors. This study was to assess and to compare the antigen-independent pharmacokinetics of anti-CD22 ADCs with uncleavable linkers (anti-CD22-MCC-DM1 and anti-CD22-MC-MMAF) and cleavable linkers (anti-CD22-SPP-DM1 and anti-CD22-vc-MMAE) in rats, and to support a pilot rat safety study. Following a single IV dose, the anti-CD22 ADCs exhibited a biphasic disposition profile. The conjugates with cleavable linkers had faster clearance compared to those with uncleavable linkers (59.4 mL/day/kg for anti-CD22-SPP-DM1 vs. 18.0 mL/day/kg for anti-CD22-MCC-DM1). The faster clearance for anti-CD22 ADCs with cleavable linker has also been observed with other ADCs (different target). In addition, it was found that free DM1 in plasma that was deconjugated from anti-CD22-SPP-DM1 had ∼70 fold higher exposure compared with that from anti-CD22-MCC-DM1 (area under curve (AUC) for free DM1 in plasma: 562 day*ng/mL for anti-CD22-SPP-DM1 vs. 8.18 day*ng/mL for anti-CD22-MCC-DM1). Furthermore, anti-CD22-SPP-DM1 had a different DM1 release profile compared with anti-CD22-MCC-DM1 when incubated with human plasma in vitro. Maximum concentrations of free DM1 were reached at ∼6 hr and ∼24 hr for anti-CD22-SPP-DM1 and anti-CD22-MCC-DM1, respectively. These observations were consistent with the safety findings in rats: anti-CD22-SPP-DM1 had greater toxicity (body weight loss, renal toxicity) compared with anti-CD22-MCC-DM1. The data described here indicate that the anti-CD22 ADCs with uncleavable linkers are cleared slower than, and have a better safety profile than the conjugates with cleavable linkers.</jats:p> |
| doi_str_mv | 10.1182/blood.v110.11.2361.2361 |
| facet_avail | Online, Free |
| finc_class_facet | Biologie, Medizin, Chemie und Pharmazie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52MTEwLjExLjIzNjEuMjM2MQ |
| imprint | American Society of Hematology, 2007 |
| imprint_str_mv | American Society of Hematology, 2007 |
| institution | DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-D161, DE-Zwi2, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1 |
| issn | 0006-4971, 1528-0020 |
| issn_str_mv | 0006-4971, 1528-0020 |
| language | English |
| last_indexed | 2024-03-01T11:16:37.632Z |
| match_str | xie2007pharmacokineticsofanticd22antibodyconjugateswithuncleavableandcleavablelinkersinrats |
| mega_collection | American Society of Hematology (CrossRef) |
| physical | 2361-2361 |
| publishDate | 2007 |
| publishDateSort | 2007 |
| publisher | American Society of Hematology |
| record_format | ai |
| recordtype | ai |
| series | Blood |
| source_id | 49 |
| spelling | Xie, Dong Deng, Rong Baudys, Jakub Chan, Pam Dere, Randy Ebens, Allen Fielder, Paul Fuji, Reina Gray, Alane Hung, Catherine Iyer, Suhas McKeever, Kathleen Kenrick, Margaret Leach, Will Polson, Andrew Saad, Ola Stephan, Jean-Philippe Shen, Ben Quan Tibbitts, Jay Yu, Shang-Fan Prabhu, Saileta 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v110.11.2361.2361 <jats:title>Abstract</jats:title> <jats:p>CD22 is a B cell specific antigen and is expressed in Non-Hodgkin lymphoma (NHL) with limited expression on normal tissues. Currently, we are evaluating anti-CD22 antibody drug conjugates (anti-CD22 ADC) consisting of a humanized monoclonal IgG antibody conjugated to mitotic inhibitors such as DM1 (a maytansinoid), Monomethylauristatin F (MMAF), or Monomethylauristatin E (MMAE). The antibody binds to human and cynomolgus monkey CD22, but does not bind to rodent CD22. The cytotoxic drugs were conjugated to the antibody via uncleavable linkers (MCC-DM1, MC-MMAF) or cleavable linkers (SPP-DM1, vc-MMAE). These conjugates have demonstrated anti-tumor activity in mouse xenograft models of human B-cell tumors. This study was to assess and to compare the antigen-independent pharmacokinetics of anti-CD22 ADCs with uncleavable linkers (anti-CD22-MCC-DM1 and anti-CD22-MC-MMAF) and cleavable linkers (anti-CD22-SPP-DM1 and anti-CD22-vc-MMAE) in rats, and to support a pilot rat safety study. Following a single IV dose, the anti-CD22 ADCs exhibited a biphasic disposition profile. The conjugates with cleavable linkers had faster clearance compared to those with uncleavable linkers (59.4 mL/day/kg for anti-CD22-SPP-DM1 vs. 18.0 mL/day/kg for anti-CD22-MCC-DM1). The faster clearance for anti-CD22 ADCs with cleavable linker has also been observed with other ADCs (different target). In addition, it was found that free DM1 in plasma that was deconjugated from anti-CD22-SPP-DM1 had ∼70 fold higher exposure compared with that from anti-CD22-MCC-DM1 (area under curve (AUC) for free DM1 in plasma: 562 day*ng/mL for anti-CD22-SPP-DM1 vs. 8.18 day*ng/mL for anti-CD22-MCC-DM1). Furthermore, anti-CD22-SPP-DM1 had a different DM1 release profile compared with anti-CD22-MCC-DM1 when incubated with human plasma in vitro. Maximum concentrations of free DM1 were reached at ∼6 hr and ∼24 hr for anti-CD22-SPP-DM1 and anti-CD22-MCC-DM1, respectively. These observations were consistent with the safety findings in rats: anti-CD22-SPP-DM1 had greater toxicity (body weight loss, renal toxicity) compared with anti-CD22-MCC-DM1. The data described here indicate that the anti-CD22 ADCs with uncleavable linkers are cleared slower than, and have a better safety profile than the conjugates with cleavable linkers.</jats:p> Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. Blood |
| spellingShingle | Xie, Dong, Deng, Rong, Baudys, Jakub, Chan, Pam, Dere, Randy, Ebens, Allen, Fielder, Paul, Fuji, Reina, Gray, Alane, Hung, Catherine, Iyer, Suhas, McKeever, Kathleen, Kenrick, Margaret, Leach, Will, Polson, Andrew, Saad, Ola, Stephan, Jean-Philippe, Shen, Ben Quan, Tibbitts, Jay, Yu, Shang-Fan, Prabhu, Saileta, Blood, Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats., Cell Biology, Hematology, Immunology, Biochemistry |
| title | Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_full | Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_fullStr | Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_full_unstemmed | Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_short | Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| title_sort | pharmacokinetics of anti-cd22 antibody conjugates with uncleavable and cleavable linkers in rats. |
| title_unstemmed | Pharmacokinetics of Anti-CD22 Antibody Conjugates with Uncleavable and Cleavable Linkers in Rats. |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood.v110.11.2361.2361 |