LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article ; Online: Therapeutic potential of SGN-CD19B, a PBD-based anti-CD19 drug conjugate, for treatment of B-cell malignancies.

Ryan, Maureen C / Palanca-Wessels, Maria Corinna / Schimpf, Brian / Gordon, Kristine A / Kostner, Heather / Meyer, Brad / Yu, Changpu / Van Epps, Heather A / Benjamin, Dennis

Blood

2017 Volume 130, Issue 18, Page(s) 2018–2026

Abstract: Patients with relapsed/refractory B-cell malignancies such as non-Hodgkin lymphoma (B-NHL) or acute lymphoblastic leukemia have a poor prognosis. Despite measurable clinical activity with new targeted therapies, many patients do not achieve a complete or ...

Abstract	Patients with relapsed/refractory B-cell malignancies such as non-Hodgkin lymphoma (B-NHL) or acute lymphoblastic leukemia have a poor prognosis. Despite measurable clinical activity with new targeted therapies, many patients do not achieve a complete or durable response suggesting an opportunity to improve upon existing therapies. Here we describe SGN-CD19B, a pyrrolobenzodiazepine (PBD)-based anti-CD19 antibody drug conjugate (ADC) being investigated for treatment of B-cell malignancies, which has improved potency compared with other ADCs. CD19-expressing tumor cells rapidly internalize SGN-CD19B, and the released PBD drug induces DNA damage, resulting in G2/M cell cycle arrest and cell death. SGN-CD19B demonstrated activity against a broad panel of malignant B-cell lines and induced durable regressions in mice bearing xenografts derived from these B-cell malignancies. A single dose of SGN-CD19B induced durable regressions at 300 μg/kg (3 μg/kg drug equivalents); combination with rituximab decreased the curative dose to 100 μg/kg (1 μg/kg drug equivalents). These doses are significantly lower than the level of drug required with other ADC payloads. In cynomolgus monkeys, SGN-CD19B effectively depleted CD20
MeSH term(s)	Animals ; Antibodies/pharmacology ; Antibodies/therapeutic use ; Antigens, CD19/metabolism ; Benzodiazepines/chemistry ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cytotoxicity, Immunologic/drug effects ; Humans ; Lymphoma, B-Cell/drug therapy ; Lymphoma, B-Cell/pathology ; Macaca fascicularis ; Mice, SCID ; Pyrroles/chemistry ; Xenograft Model Antitumor Assays
Chemical Substances	Antibodies ; Antigens, CD19 ; Pyrroles ; SGN-CD19B ; pyrrolo(2,1-c)(1,4)benzodiazepine ; Benzodiazepines (12794-10-4)
Language	English
Publishing date	2017-09-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2017-04-779389
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Development of Novel Quaternary Ammonium Linkers for Antibody-Drug Conjugates.

Burke, Patrick J / Hamilton, Joseph Z / Pires, Thomas A / Setter, Jocelyn R / Hunter, Joshua H / Cochran, Julia H / Waight, Andrew B / Gordon, Kristine A / Toki, Brian E / Emmerton, Kim K / Zeng, Weiping / Stone, Ivan J / Senter, Peter D / Lyon, Robert P / Jeffrey, Scott C

Molecular cancer therapeutics

2016 Volume 15, Issue 5, Page(s) 938–945

Abstract: A quaternary ammonium-based drug-linker has been developed to expand the scope of antibody-drug conjugate (ADC) payloads to include tertiary amines, a functional group commonly present in biologically active compounds. The linker strategy was exemplified ...

Abstract	A quaternary ammonium-based drug-linker has been developed to expand the scope of antibody-drug conjugate (ADC) payloads to include tertiary amines, a functional group commonly present in biologically active compounds. The linker strategy was exemplified with a β-glucuronidase-cleavable auristatin E construct. The drug-linker was found to efficiently release free auristatin E (AE) in the presence of β-glucuronidase and provide ADCs that were highly stable in plasma. Anti-CD30 conjugates comprised of the glucuronide-AE linker were potent and immunologically specific in vitro and in vivo, displaying pharmacologic properties comparable with a carbamate-linked glucuronide-monomethylauristatin E control. The quaternary ammonium linker was then applied to a tubulysin antimitotic drug that contained an N-terminal tertiary amine that was important for activity. A glucuronide-tubulysin quaternary ammonium linker was synthesized and evaluated as an ADC payload, in which the resulting conjugates were found to be potent and immunologically specific in vitro, and displayed a high level of activity in a Hodgkin lymphoma xenograft. Furthermore, the results were superior to those obtained with a related tubulysin derivative containing a secondary amine N-terminus for conjugation using previously known linker technology. The quaternary ammonium linker represents a significant advance in linker technology, enabling stable conjugation of payloads with tertiary amine residues. Mol Cancer Ther; 15(5); 938-45. ©2016 AACR.
MeSH term(s)	Ammonium Compounds/chemistry ; Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/pharmacology ; Cell Line, Tumor ; Disease Models, Animal ; Drug Liberation ; Drug Stability ; Humans ; Immunoconjugates/chemistry ; Immunoconjugates/pharmacokinetics ; Immunoconjugates/pharmacology ; Kinetics ; Mice ; Molecular Structure ; Protein Binding ; Rats ; Tubulin ; Xenograft Model Antitumor Assays
Chemical Substances	Ammonium Compounds ; Antibodies, Monoclonal ; Immunoconjugates ; Tubulin
Language	English
Publishing date	2016-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-16-0038
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5750: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker.

Oflazoglu, Ezogelin / Stone, Ivan J / Gordon, Kristine / Wood, Christopher G / Repasky, Elizabeth A / Grewal, Iqbal S / Law, Che-Leung / Gerber, Hans-Peter

Clinical cancer research : an official journal of the American Association for Cancer Research

2008 Volume 14, Issue 19, Page(s) 6171–6180

Abstract: Purpose: The antitubulin agent monomethyl auristatin F (MMAF) induces potent antitumor effects when conjugated via protease cleavable linkers to antibodies targeting internalizing, tumor-specific cell surface antigens. Humanized 1F6 (h1F6) is a ... ...

Abstract	Purpose: The antitubulin agent monomethyl auristatin F (MMAF) induces potent antitumor effects when conjugated via protease cleavable linkers to antibodies targeting internalizing, tumor-specific cell surface antigens. Humanized 1F6 (h1F6) is a humanized monoclonal antibody targeting CD70, a member of the tumor necrosis factor family that is expressed on hematologic malignancies and carcinomas. Here, we tested h1F6-maleimidocaproyl (mc) MMAF conjugates, consisting of an uncleavable mc linker, for their ability to interfere with the growth of CD70-positive carcinomas. Experimental design: To evaluate the optimal drug per antibody ratio, we conjugated either four or eight MMAF molecules to the cysteines that comprise the interchain disulfides of h1F6 and determined antitumor activities in vitro and in xenografted mice. The tumor types tested included glioblastoma, patient-derived renal cell carcinoma (RCC) cell isolates, and standard RCC tumor cell lines. Results: All h1F6-mcMMAF conjugates potently interfered with the growth of all carcinomas in vitro and resulted in complete responses of RCC tumors implanted orthotopically or s.c. in mice. In vitro, h1F6-mcMMAF(8) was generally more potent than h1F6-mcMMAF(4). However, h1F6-mcMMAF(4) displayed equal or better efficacy than h1F6-mcMMAF(8) when administered to tumor-bearing mice. Conclusions: We showed that h1F6-mcMMAF conjugates inhibited the growth of human carcinomas and that increased drug loading, while improving potency in vitro, did not substantially affect the pharmacodynamic and pharmacokinetic properties in vivo. Based on these findings, h1F6-mcMMAF(4), designated SGN-75, has been identified as a potential antibody-drug conjugate for clinical development.
MeSH term(s)	Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal, Humanized/chemistry ; Antibodies, Monoclonal, Humanized/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; CD27 Ligand/chemistry ; CD27 Ligand/immunology ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/pathology ; Cell Line, Tumor ; Disulfides/chemistry ; Glioblastoma/drug therapy ; Glioblastoma/pathology ; Humans ; Inhibitory Concentration 50 ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/pathology ; Mice ; Neoplasm Transplantation ; Oligopeptides/chemistry ; Oligopeptides/pharmacology ; Tubulin/chemistry ; Tubulin Modulators/chemistry
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; CD27 Ligand ; Disulfides ; Oligopeptides ; SGN-75 antibody-drug conjugate ; Tubulin ; Tubulin Modulators ; monomethylauristatin F
Language	English
Publishing date	2008-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-08-0916
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4223: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30.

Oflazoglu, Ezogelin / Stone, Ivan J / Gordon, Kristine A / Grewal, Iqbal S / van Rooijen, Nico / Law, Che-Leung / Gerber, Hans-Peter

Blood

2007 Volume 110, Issue 13, Page(s) 4370–4372

Abstract: Increased expression of CD30 is associated with a variety of hematologic malignancies, including Hodgkin disease (HD) and anaplastic large cell lymphoma (ALCL). The anti-CD30 monoclonal antibody SGN-30 induces direct antitumor activity by promoting ... ...

Abstract	Increased expression of CD30 is associated with a variety of hematologic malignancies, including Hodgkin disease (HD) and anaplastic large cell lymphoma (ALCL). The anti-CD30 monoclonal antibody SGN-30 induces direct antitumor activity by promoting growth arrest and DNA fragmentation of CD30(+) tumor cells. In this study, we investigated the contributions of Fc-mediated effector cell functions to SGN-30 activity. We determined that antibody-dependent cellular phagocytosis, mediated by macrophages, to contribute significantly to antitumor activity in vitro. To delineate the identity of the host effector cells involved in mediating antitumor activity in vivo, we studied the effects of effector cell ablation in a disseminated model of HD (L540cy). Depletion of macrophages markedly reduced efficacy of SGN-30, demonstrating that macrophages contribute significantly to SGN-30 efficacy in this model. These findings may have implications for patient stratification or combination treatment strategies in clinical trials conducted with SGN-30 in HD and ALCL.
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Antibody-Dependent Cell Cytotoxicity/drug effects ; Cell Line, Tumor ; Hodgkin Disease/therapy ; Humans ; Ki-1 Antigen/immunology ; Macrophages/immunology ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Phagocytosis/drug effects ; Transplantation, Heterologous
Chemical Substances	Antibodies, Monoclonal ; Ki-1 Antigen ; SGN-30 monoclonal antibody (C67ORA155P)
Language	English
Publishing date	2007-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2007-06-097014
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Preclinical characterization of SGN-70, a humanized antibody directed against CD70.

McEarchern, Julie A / Smith, Leia M / McDonagh, Charlotte F / Klussman, Kerry / Gordon, Kristine A / Morris-Tilden, Carol A / Duniho, Steven / Ryan, Maureen / Boursalian, Tamar E / Carter, Paul J / Grewal, Iqbal S / Law, Che-Leung

Clinical cancer research : an official journal of the American Association for Cancer Research

2008 Volume 14, Issue 23, Page(s) 7763–7772

Abstract: Purpose: CD70 (CD27L) is a member of the tumor necrosis factor family aberrantly expressed on a number of hematologic malignancies and some carcinomas. CD70 expression on malignant cells coupled with its highly restricted expression on normal cells ... ...

Abstract	Purpose: CD70 (CD27L) is a member of the tumor necrosis factor family aberrantly expressed on a number of hematologic malignancies and some carcinomas. CD70 expression on malignant cells coupled with its highly restricted expression on normal cells makes CD70 an attractive target for monoclonal antibody (mAb)-based therapies. We developed a humanized anti-CD70 antibody, SGN-70, and herein describe the antitumor activities of this mAb. Experimental design: CD70 expression on primary tumors was evaluated by immunohistochemical staining of Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, and renal cell carcinoma tissue microarrays. The CD70-binding and cytotoxic activities of SGN-70 were tested in vitro using a number of cell-based assays. The in vivo antitumor properties of SGN-70 were tested in severe combined immunodeficient mice bearing disseminated lymphoma and multiple myeloma xenografts. Mechanism-of-action studies were conducted using SGN-70v, a variant mAb with equivalent target-binding activity but impaired Fcgamma receptor binding compared with SGN-70. Results: Immunohistochemical analysis identified CD70 expression on approximately 40% of multiple myeloma isolates and confirmed CD70 expression on a high percentage of Hodgkin lymphoma Reed-Sternberg cells, non-Hodgkin lymphoma, and renal cell carcinoma tumors. SGN-70 lysed CD70+ tumor cells via Fc-dependent functions, including antibody-dependent cellular cytotoxicity and phagocytosis and complement fixation. In vivo, SGN-70 treatment significantly decreased tumor burden and prolonged survival of tumor-bearing mice. Conclusions: SGN-70 is a novel humanized IgG1 mAb undergoing clinical development for the treatment of CD70+ cancers. SGN-70 possesses Fc-dependent antibody effector functions and mediates antitumor activity in vivo.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibody Affinity ; Antineoplastic Agents/immunology ; Antineoplastic Agents/pharmacology ; CD27 Ligand/immunology ; CD27 Ligand/metabolism ; Carcinoma, Renal Cell/immunology ; Carcinoma, Renal Cell/metabolism ; Humans ; Immunohistochemistry ; Kidney Neoplasms/immunology ; Kidney Neoplasms/metabolism ; Lymphoma/immunology ; Lymphoma/metabolism ; Mice ; Mice, SCID ; Tissue Array Analysis ; Xenograft Model Antitumor Assays
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents ; CD27 Ligand ; CD70 protein, human
Language	English
Publishing date	2008-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-08-0493
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4223: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Lysosomal Trafficking and Cysteine Protease Metabolism Confer Target-specific Cytotoxicity by Peptide-linked Anti-CD30-Auristatin Conjugates

Sutherland, May S. Kung / Sanderson, Russell J / Gordon, Kristine A / Andreyka, Jamie / Cerveny, Charles G / Yu, Changpu / Lewis, Timothy S / Meyer, Damon L / Zabinski, Roger F / Doronina, Svetlana O / Senter, Peter D / Law, Che-Leung / Wahl, Alan F

Journal of biological chemistry. 2006 Apr. 14, v. 281, no. 15

2006

Abstract: The chimeric anti-CD30 monoclonal antibody cAC10, linked to the antimitotic agents monomethyl auristatin E (MMAE) or F (MMAF), produces potent and highly CD30-selective anti-tumor activity in vitro and in vivo. These drugs are appended via a valine- ... ...

Abstract	The chimeric anti-CD30 monoclonal antibody cAC10, linked to the antimitotic agents monomethyl auristatin E (MMAE) or F (MMAF), produces potent and highly CD30-selective anti-tumor activity in vitro and in vivo. These drugs are appended via a valine-citrulline (vc) dipeptide linkage designed for high stability in serum and conditional cleavage and putative release of fully active drugs by lysosomal cathepsins. To characterize the biochemical processes leading to effective drug delivery, we examined the intracellular trafficking, internalization, and metabolism of the parent antibody and two antibody-drug conjugates, cAC10vc-MMAE and cAC10vc-MMAF, following CD30 surface antigen interaction with target cells. Both cAC10 and its conjugates bound to target cells and internalized in a similar manner. Subcellular fractionation and immunofluorescence studies demonstrated that the antibody and antibody-drug conjugates entering target cells migrated to the lysosomes. Trafficking of both species was blocked by inhibitors of clathrin-mediated endocytosis, suggesting that drug conjugation does not alter the fate of antibody-antigen complexes. Incubation of cAC10vc-MMAE or cAC10vc-MMAF with purified cathepsin B or with enriched lysosomal fractions prepared by subcellular fractionation resulted in the release of active, free drug. Cysteine protease inhibitors, but not aspartic or serine protease inhibitors, blocked antibody-drug conjugate metabolism and the ensuing cytotoxicity of target cells and yielded enhanced intracellular levels of the intact conjugates. These findings suggest that in addition to trafficking to the lysosomes, cathepsin B and perhaps other lysosomal cysteine proteases are requisite for drug release and provide a mechanistic basis for developing antibody-drug conjugates cleavable by intracellular proteases for the targeted delivery of anti-cancer therapeutics.
Language	English
Dates of publication	2006-0414
Size	p. 10540-10547.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 65/118: Show issues
Z 6.2: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates.

Sutherland, May S Kung / Sanderson, Russell J / Gordon, Kristine A / Andreyka, Jamie / Cerveny, Charles G / Yu, Changpu / Lewis, Timothy S / Meyer, Damon L / Zabinski, Roger F / Doronina, Svetlana O / Senter, Peter D / Law, Che-Leung / Wahl, Alan F

The Journal of biological chemistry

2006 Volume 281, Issue 15, Page(s) 10540–10547

Abstract	The chimeric anti-CD30 monoclonal antibody cAC10, linked to the antimitotic agents monomethyl auristatin E (MMAE) or F (MMAF), produces potent and highly CD30-selective anti-tumor activity in vitro and in vivo. These drugs are appended via a valine-citrulline (vc) dipeptide linkage designed for high stability in serum and conditional cleavage and putative release of fully active drugs by lysosomal cathepsins. To characterize the biochemical processes leading to effective drug delivery, we examined the intracellular trafficking, internalization, and metabolism of the parent antibody and two antibody-drug conjugates, cAC10vc-MMAE and cAC10vc-MMAF, following CD30 surface antigen interaction with target cells. Both cAC10 and its conjugates bound to target cells and internalized in a similar manner. Subcellular fractionation and immunofluorescence studies demonstrated that the antibody and antibody-drug conjugates entering target cells migrated to the lysosomes. Trafficking of both species was blocked by inhibitors of clathrin-mediated endocytosis, suggesting that drug conjugation does not alter the fate of antibody-antigen complexes. Incubation of cAC10vc-MMAE or cAC10vc-MMAF with purified cathepsin B or with enriched lysosomal fractions prepared by subcellular fractionation resulted in the release of active, free drug. Cysteine protease inhibitors, but not aspartic or serine protease inhibitors, blocked antibody-drug conjugate metabolism and the ensuing cytotoxicity of target cells and yielded enhanced intracellular levels of the intact conjugates. These findings suggest that in addition to trafficking to the lysosomes, cathepsin B and perhaps other lysosomal cysteine proteases are requisite for drug release and provide a mechanistic basis for developing antibody-drug conjugates cleavable by intracellular proteases for the targeted delivery of anti-cancer therapeutics.
MeSH term(s)	Antibodies/chemistry ; Antigens, CD20/chemistry ; Antineoplastic Agents/pharmacology ; Blotting, Western ; Cathepsin B/chemistry ; Cell Line ; Cysteine Endopeptidases/chemistry ; Cysteine Proteinase Inhibitors/pharmacology ; Dose-Response Relationship, Drug ; Endocytosis ; Endopeptidases/chemistry ; Flow Cytometry ; Humans ; Inhibitory Concentration 50 ; Ki-1 Antigen/chemistry ; Lysosomes/metabolism ; Microscopy, Fluorescence ; Models, Chemical ; Oligopeptides/chemistry ; Peptide Hydrolases/chemistry ; Peptides/chemistry ; Protein Binding ; Subcellular Fractions/metabolism ; Temperature ; Time Factors ; beta-Galactosidase/metabolism
Chemical Substances	Antibodies ; Antigens, CD20 ; Antineoplastic Agents ; Cysteine Proteinase Inhibitors ; Ki-1 Antigen ; Oligopeptides ; Peptides ; soblidotin (DQC51A0WQH) ; beta-Galactosidase (EC 3.2.1.23) ; Endopeptidases (EC 3.4.-) ; Peptide Hydrolases (EC 3.4.-) ; Cysteine Endopeptidases (EC 3.4.22.-) ; Cathepsin B (EC 3.4.22.1)
Language	English
Publishing date	2006-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M510026200
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities.

McEarchern, Julie A / Oflazoglu, Ezogelin / Francisco, Leigh / McDonagh, Charlotte F / Gordon, Kristine A / Stone, Ivan / Klussman, Kerry / Turcott, Eileen / van Rooijen, Nico / Carter, Paul / Grewal, Iqbal S / Wahl, Alan F / Law, Che-Leung

Blood

2006 Volume 109, Issue 3, Page(s) 1185–1192

Abstract: Antigens expressed on malignant cells in the absence of significant expression on normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a TNF superfamily member whose normal expression is highly restricted but is aberrantly ... ...

Abstract	Antigens expressed on malignant cells in the absence of significant expression on normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a TNF superfamily member whose normal expression is highly restricted but is aberrantly expressed in hematologic malignancies including non-Hodgkin lymphoma (NHL), Hodgkin disease, and multiple myeloma. In addition, solid tumors such as renal cell carcinoma, nasopharyngeal carcinoma, thymic carcinoma, meduloblastoma, and glioblastoma express high levels of this antigen. To functionally target CD70-expressing cancers, a murine anti-CD70 monoclonal antibody was engineered to contain human IgG1 constant domains. The engineered antibody retained the binding specificity of the murine parent monoclonal antibody and was shown to induce Fc-mediated effector functions including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis in vitro. Further, administration of this antibody significantly prolonged survival of severe combined immunodeficient (SCID) mice bearing CD70+ disseminated human NHL xenografts. Survival of these mice was dependent upon the activity of resident effector cells including neutrophils, macrophages, and natural killer (NK) cells. These data suggest that an anti-CD70 antibody, when engineered to contain human IgG1 constant domains, possesses effector cell-mediated antitumor activity and has potential utility for anticancer therapy.
MeSH term(s)	Animals ; Antibodies/genetics ; Antibodies/immunology ; Antibodies/therapeutic use ; Antibody Specificity ; Antibody-Dependent Cell Cytotoxicity ; Antineoplastic Agents ; CD27 Ligand/immunology ; Cell Line, Tumor ; Complement System Proteins ; Humans ; Immune System/cytology ; Immunoglobulin G ; Lymphoma, Non-Hodgkin/therapy ; Mice ; Mice, SCID ; Phagocytosis ; Protein Engineering/methods ; Survival Rate ; Transplantation, Heterologous
Chemical Substances	Antibodies ; Antineoplastic Agents ; CD27 Ligand ; Immunoglobulin G ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2006-10-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2006-07-034017
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Preclinical antilymphoma activity of a humanized anti-CD40 monoclonal antibody, SGN-40.

Law, Che-Leung / Gordon, Kristine A / Collier, John / Klussman, Kerry / McEarchern, Julie A / Cerveny, Charles G / Mixan, Bruce J / Lee, Wyne P / Lin, Zhonghau / Valdez, Patricia / Wahl, Alan F / Grewal, Iqbal S

Cancer research

2005 Volume 65, Issue 18, Page(s) 8331–8338

Abstract: SGN-40 is a humanized IgG1 antihuman CD40 that is currently in a phase I clinical trial for the treatment of multiple myeloma. As surface CD40 expression on B-lineage cells is maintained from pro-B cells to plasma cells, SGN-40 may be applicable to ... ...

Abstract	SGN-40 is a humanized IgG1 antihuman CD40 that is currently in a phase I clinical trial for the treatment of multiple myeloma. As surface CD40 expression on B-lineage cells is maintained from pro-B cells to plasma cells, SGN-40 may be applicable to treatment of other B-cell neoplasias, including non-Hodgkin's lymphoma. In this study, we examined potential in vitro and in vivo anti-B-lineage lymphoma activity of SGN-40. Recombinant SGN-40 was expressed and purified from Chinese hamster ovary cells and characterized based on binding affinity, specificity, and normal B-cell stimulation. The ability of SGN-40 to target neoplastic B cells was examined in vitro by proliferation inhibition, cytotoxicity, and antibody-dependent cell cytotoxicity assays and in vivo by human lymphoma xenograft models. Recombinant SGN-40 showed high affinity, Kd of approximately 1 nmol/L, and specific binding to CD40. Whereas SGN-40 was a weak agonist in stimulating normal B-cell proliferation in the absence of IL-4 and CD40L, it delivered potent proliferation inhibitory and apoptotic signals to, and mediated antibody-dependent cytotoxicity against, a panel of high-grade B-lymphoma lines. These in vitro antilymphoma effects were extended to disseminated and s.c. xenograft CD40 tumor models. In these xenograft models, the antitumor activity of SGN-40 was comparable with that of rituximab. The preclinical in vitro and in vivo antilymphoma activity of SGN-40 observed in this study provides a rationale for the clinical testing of SGN-40 in the treatment of CD40+ B-lineage lymphomas.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibody-Dependent Cell Cytotoxicity ; Apoptosis/drug effects ; Apoptosis/immunology ; B-Lymphocytes/cytology ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; CD40 Antigens/immunology ; Caspase 3 ; Caspases/metabolism ; Cell Growth Processes/drug effects ; Cell Growth Processes/immunology ; Cell Line, Tumor ; Enzyme Activation ; Humans ; Immunoglobulin G/immunology ; Immunoglobulin G/pharmacology ; Lymphoma, B-Cell/immunology ; Lymphoma, B-Cell/pathology ; Lymphoma, B-Cell/therapy ; Mice ; Mice, SCID ; Xenograft Model Antitumor Assays
Chemical Substances	Antibodies, Monoclonal ; CD40 Antigens ; Immunoglobulin G ; CASP3 protein, human (EC 3.4.22.-) ; Casp3 protein, mouse (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2005-09-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-05-0095
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.135/5: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Design, synthesis, and in vitro evaluation of dipeptide-based antibody minor groove binder conjugates.

Jeffrey, Scott C / Torgov, Michael Y / Andreyka, Jamie B / Boddington, Laura / Cerveny, Charles G / Denny, William A / Gordon, Kristine A / Gustin, Darin / Haugen, Jennifer / Kline, Toni / Nguyen, Minh T / Senter, Peter D

Journal of medicinal chemistry

2005 Volume 48, Issue 5, Page(s) 1344–1358

Abstract: Antibody-drug conjugates (ADCs) were prepared consisting of DNA minor groove binder drugs (MGBs) attached to monoclonal antibodies (mAbs) through peptide linkers designed to release drugs inside the lysosomes of target cells. The site of linker ... ...

Abstract	Antibody-drug conjugates (ADCs) were prepared consisting of DNA minor groove binder drugs (MGBs) attached to monoclonal antibodies (mAbs) through peptide linkers designed to release drugs inside the lysosomes of target cells. The site of linker attachment on the MGB was at the 5-position on the B-ring, since model studies showed that attachment of an electron-withdrawing group (i.e., acyl, carbamoyl) at this position increased the stability of the molecule. Because of the hydrophobic nature of the MGBs, several measures were required to overcome their tendencies to induce mAb aggregation upon conjugation. This is exemplified in the series of ADCs containing the amino-CBI drug 1. Initial adducts were prepared using the peptide sequence valine-citrulline, attached to a self-immolative para-aminobenzyl carbamate spacer. The resulting ADCs were completely aggregated. Removal of the self-immolative spacer, introduction of a more hydrophilic valine-lysine sequence, and incorporation of a tetraethyleneglycol unit between the mAb and the peptide resulted in conjugates that were nonaggregated, even with as many as eight drugs per mAb. These results were extended to include the hydroxy aza-CBI drug 2, which was linked to the valine-lysine sequence through a para-aminobenzyl ether self-immolative spacer. The resulting mAb conjugates were monomeric and released the hydroxy aza-CBI drug upon treatment with human cathepsin B. In vitro cytotoxicity assays established that the mAb-MGB drug conjugates were highly cytotoxic and effected immunologically specific cell kill at subsaturating doses. The results provide a general strategy for MGB prodrug design and illustrate the importance of linker hydrophilicity in making nonaggregated, active mAb-MGB conjugates.
MeSH term(s)	Animals ; Antibodies, Monoclonal/chemistry ; Antineoplastic Agents, Alkylating/chemical synthesis ; Antineoplastic Agents, Alkylating/chemistry ; Antineoplastic Agents, Alkylating/pharmacology ; Aza Compounds/chemical synthesis ; Aza Compounds/chemistry ; Aza Compounds/pharmacology ; Cathepsin B/chemistry ; Cell Line, Tumor ; Cyclopropanes/chemical synthesis ; Cyclopropanes/chemistry ; Cyclopropanes/pharmacology ; DNA/chemistry ; Dipeptides/chemistry ; Drug Design ; Drug Screening Assays, Antitumor ; Humans ; Immunoconjugates/chemistry ; Indoles/chemical synthesis ; Indoles/chemistry ; Indoles/pharmacology ; Mice ; Structure-Activity Relationship
Chemical Substances	1,2,9,9a-tetrahydrocyclopropa(c)benz(e)indol-4-one ; Antibodies, Monoclonal ; Antineoplastic Agents, Alkylating ; Aza Compounds ; Cyclopropanes ; Dipeptides ; Immunoconjugates ; Indoles ; DNA (9007-49-2) ; Cathepsin B (EC 3.4.22.1)
Language	English
Publishing date	2005-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/jm040137q
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MB 1: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Your last searches

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito