Antigen-specific activity of carcinoma-reactive BR64-doxorubicin conjugates evaluated in vitro and in human tumor xenograft models
The anticarcinoma antibody BR64 was conjugated to a doxorubicin derivative, doxorubicin 13-[3-(2-pyridyldithio)propionyl]hydrazone, and the resulting conjugates (BR64-DOX) were evaluated for activity and immunological specificity in vitro and in human tumor xenograft models. The BR64-DOX immunoconjugates retained immunoreactivity and cytotoxicity and demonstrated antigen-specific cytotoxicity in vitro. The potency of BR64-DOX immunoconjugates in vitro was related to the drug:monoclonal antibody mole ratio of the conjugates. The antitumor activity of BR64-DOX conjugates was consistently superior to the maximal activity obtained with the parent drug, doxorubicin (DOX), in established human lung and human breast carcinoma xenograft models. The superior antitumor activity of BR64-DOX conjugates was reflected both in tumor growth inhibition and in regressions and cures of established tumors following the administration of tolerated doses of BR64-DOX. The antitumor activity of BR64-DOX conjugates was not the result of synergism between monoclonal antibody BR64 and DOX, because mixtures consisting of monoclonal antibody and optimized DOX were not more active than an equivalent dose of DOX administered alone. The antitumor activity of BR64-DOX conjugates was antigen specific; equivalent doses of nonbinding isotype-matched conjugates were not active against established tumor xenografts.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1992 |
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| Erschienen: |
1992 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
|---|---|
| Enthalten in: |
Cancer research - 52(1992), 20 vom: 15. Okt., Seite 5693-700 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Trail, P A [VerfasserIn] |
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| Themen: |
80168379AG |
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| Anmerkungen: |
Date Completed 10.11.1992 Date Revised 21.11.2013 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM013642359 |
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|---|---|---|---|
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| 003 | DE-627 | ||
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| 008 | 231221s1992 xx ||||| 00| ||eng c | ||
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| 041 | |a eng | ||
| 100 | 1 | |a Trail, P A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Antigen-specific activity of carcinoma-reactive BR64-doxorubicin conjugates evaluated in vitro and in human tumor xenograft models |
| 264 | 1 | |c 1992 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 10.11.1992 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The anticarcinoma antibody BR64 was conjugated to a doxorubicin derivative, doxorubicin 13-[3-(2-pyridyldithio)propionyl]hydrazone, and the resulting conjugates (BR64-DOX) were evaluated for activity and immunological specificity in vitro and in human tumor xenograft models. The BR64-DOX immunoconjugates retained immunoreactivity and cytotoxicity and demonstrated antigen-specific cytotoxicity in vitro. The potency of BR64-DOX immunoconjugates in vitro was related to the drug:monoclonal antibody mole ratio of the conjugates. The antitumor activity of BR64-DOX conjugates was consistently superior to the maximal activity obtained with the parent drug, doxorubicin (DOX), in established human lung and human breast carcinoma xenograft models. The superior antitumor activity of BR64-DOX conjugates was reflected both in tumor growth inhibition and in regressions and cures of established tumors following the administration of tolerated doses of BR64-DOX. The antitumor activity of BR64-DOX conjugates was not the result of synergism between monoclonal antibody BR64 and DOX, because mixtures consisting of monoclonal antibody and optimized DOX were not more active than an equivalent dose of DOX administered alone. The antitumor activity of BR64-DOX conjugates was antigen specific; equivalent doses of nonbinding isotype-matched conjugates were not active against established tumor xenografts | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neoplasm |2 NLM | |
| 650 | 7 | |a Antigens, Neoplasm |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Immunotoxins |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 700 | 1 | |a Willner, D |e verfasserin |4 aut | |
| 700 | 1 | |a Lasch, S J |e verfasserin |4 aut | |
| 700 | 1 | |a Henderson, A J |e verfasserin |4 aut | |
| 700 | 1 | |a Greenfield, R S |e verfasserin |4 aut | |
| 700 | 1 | |a King, D |e verfasserin |4 aut | |
| 700 | 1 | |a Zoeckler, M E |e verfasserin |4 aut | |
| 700 | 1 | |a Braslawsky, G R |e verfasserin |4 aut | |
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| 952 | |d 52 |j 1992 |e 20 |b 15 |c 10 |h 5693-700 | ||