Delving into the Latest Updates on Anti-APO-1 monoclonal antibody(Centocor) with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

FasR

Mechanism

FasR inhibitors(Apoptosis-mediating surface antigen FAS inhibitors)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Rheumatoid Arthritis

Originator Organization

Centocor, Inc.

Active Organization-

Inactive Organization

Argenes, Inc.

AYUMI Pharmaceutical Corp.Startup

Johnson & Johnson

+ [1]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Author: Hendricks, Angela ; Chalouni, Cecile ; Chiu, Cecilia ; Schutten, Melissa M. ; Liang, Wei-Ching ; Sadowsky, Jack ; Zheng, Bing ; Vij, Rajesh ; Polson, Andrew G. ; Flygare, John ; Clark, Vanessa ; Pillow, Thomas ; Lee, Genee Y. ; Yu, Shang-Fan ; del Rosario, Geoffrey ; Chu, Wayne ; Leong, Steven R. ; Poon, Kirsten Achilles ; Wu, Yan

AbstractPurpose:The treatment of acute myeloid leukemia (AML) has not significantly changed in 40 years. Cytarabine- and anthracycline-based chemotherapy induction regimens (7 + 3) remain the standard of care, and most patients have poor long-term survival. The reapproval of Mylotarg, an anti-CD33–calicheamicin antibody–drug conjugate (ADC), has demonstrated ADCs as a clinically validated option to enhance the effectiveness of induction therapy. We are interested in developing a next-generation ADC for AML to improve upon the initial success of Mylotarg.Experimental Design:The expression pattern of CLL-1 and its hematopoietic potential were investigated. A novel anti–CLL-1-ADC, with a highly potent pyrrolobenzodiazepine (PBD) dimer conjugated through a self-immolative disulfide linker, was developed. The efficacy and safety profiles of this ADC were evaluated in mouse xenograft models and in cynomolgus monkeys.Results:We demonstrate that CLL-1 shares similar prevalence and trafficking properties that make CD33 an excellent ADC target for AML, but lacks expression on hematopoietic stem cells that hampers current CD33-targeted ADCs. Our anti–CLL-1-ADC is highly effective at depleting tumor cells in AML xenograft models and lacks target independent toxicities at doses that depleted target monocytes and neutrophils in cynomolgus monkeys.Conclusions:Collectively, our data suggest that an anti–CLL-1-ADC has the potential to become an effective and safer treatment for AML in humans, by reducing and allowing for faster recovery from initial cytopenias than the current generation of ADCs for AML.

01 Dec 2010·BMC Musculoskeletal DisordersQ3 · MEDICINE

ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model

Q3 · MEDICINE

ArticleOA

Author: Noriko Odani-Kawabata ; Minoru Sasano ; Tsukasa Matsubara ; Hiroshi Nakamura ; Keiko Funahashi ; Miwa Takai-Imamura ; Kusuki Nishioka ; Hiroyuki Aono ; Osamu Katsuta

BACKGROUNDThe anti-human Fas/APO-1/CD95 (Fas) mouse/human chimeric monoclonal IgM antibody ARG098 (ARG098) targets the human Fas molecule. The cytotoxic effects of ARG098 on cells isolated from RA patients, on normal cells in vitro, and on RA synovial tissue and cartilage in vivo using implanted rheumatoid tissues in an SCID mouse model (SCID-HuRAg) were investigated to examine the potential of ARG098 as a therapy for RA.METHODSARG098 binding to each cell was analyzed by cytometry. The effects of ARG098 on several cells were assessed by a cell viability assay in vitro. Effects on the RA synovium, lymphocytes, and cartilage were assessed in vivo using the SCID-HuRAg mouse model.RESULTSARG098 bound to cell surface Fas molecules, and induced apoptosis in Fas-expressing RA synoviocytes and infiltrating lymphocytes in the RA synovium in a dose-dependent manner. However, ARG098 did not affect the cell viability of peripheral blood mononuclear cells of RA patients or normal chondrocytes. ARG098 also induced apoptosis in RA synoviocytes and infiltrating lymphocytes in the RA synovium in vivo. The destruction of cartilage due to synovial invasion was inhibited by ARG098 injection in the modified SCID-HuRAg mouse model.CONCLUSIONSARG098 treatment suppressed RA synovial hyperplasia through the induction of apoptosis and prevented cartilage destruction in vivo. These results suggest that ARG098 might become a new therapy for RA.

01 Oct 2010·Nuclear Medicine and BiologyQ4 · MEDICINE

Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas

Q4 · MEDICINE

Article

Author: Yukinari Kato ; Darell D. Bigner ; Mika Kato Kaneko ; Vidyalakshmi Chandramohan ; Kazuhiko Mishima ; Michael R. Zalutsky ; Charles Pegram ; Ganesan Vaidyanathan ; Stephen T. Keir ; Chien-Tsun Kuan ; Nidhi Srivastava

INTRODUCTIONPodoplanin/aggrus is a mucin-like sialoglycoprotein that is highly expressed in malignant gliomas. Podoplanin has been reported to be a novel marker to enrich tumor-initiating cells, which are thought to resist conventional therapies and to be responsible for cancer relapse. The purpose of this study was to determine whether an anti-podoplanin antibody is suitable to target radionuclides to malignant gliomas.METHODSThe binding affinity of an anti-podoplanin antibody, NZ-1 (rat IgG(2a)), was determined by surface plasmon resonance and Scatchard analysis. NZ-1 was radioiodinated with (125)I using Iodogen [(125)I-NZ-1(Iodogen)] or N-succinimidyl 4-guanidinomethyl 3-[(131)I]iodobenzoate ([(131)I]SGMIB-NZ-1), and paired-label internalization assays of NZ-1 were performed. The tissue distribution of (125)I-NZ-1(Iodogen) and that of [(131)I]SGMIB-NZ-1 were then compared in athymic mice bearing glioblastoma xenografts.RESULTSThe dissociation constant (K(D)) of NZ-1 was determined to be 1.2 × 10(-10) M by surface plasmon resonance and 9.8 × 10(-10) M for D397MG glioblastoma cells by Scatchard analysis. Paired-label internalization assays in LN319 glioblastoma cells indicated that [(131)I]SGMIB-NZ-1 resulted in higher intracellular retention of radioactivity (26.3 ± 0.8% of initially bound radioactivity at 8 h) compared to that from the (125)I-NZ-1(Iodogen) (10.0 ± 0.1% of initially bound radioactivity at 8 h). Likewise, tumor uptake of [(131)I]SGMIB-NZ-1 (39.9 ± 8.8 %ID/g at 24 h) in athymic mice bearing D2159MG xenografts in vivo was significantly higher than that of (125)I-NZ-1(Iodogen) (29.7 ± 6.1 %ID/g at 24 h).CONCLUSIONSThe overall results suggest that an anti-podoplanin antibody NZ-1 warrants further evaluation for antibody-based therapy against glioblastoma.

100 Deals associated with Anti-APO-1 monoclonal antibody(Centocor)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Rheumatoid Arthritis	Phase 2	-	Santen SAS	-
Rheumatoid Arthritis	Phase 2	-	Argenes, Inc.	-
Rheumatoid Arthritis	Phase 2	-	AYUMI Pharmaceutical Corp.Startup	-
Rheumatoid Arthritis	Phase 2	-	Johnson & Johnson	-
Rheumatoid Arthritis	Phase 2	JP	-	-