Delving into the Latest Updates on Bivatuzumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

ANTI-CD44, anti-CD44 monoclonals

Target

CD44

Mechanism

CD44 inhibitors(CD44 antigen inhibitors)

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication-

Inactive Indication

Head and Neck NeoplasmsMammary adenocarcinomaNon-Small Cell Lung Cancer

Originator Organization

C.H. Boehringer Sohn AG & Co. KG

Active Organization-

Inactive Organization

Boehringer Ingelheim GmbHC.H. Boehringer Sohn AG & Co. KG

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 68624

Sequence Code 68628

The primary objectives of this study is to assess the safety and tolerability of intravenously (i.v.) administered 186 Rhenium-isotope (186Re)-labelled bivatuzumab and to investigate the biodistribution and pharmacokinetics of 186 Re-labelled bivatuzumab in patients with non-small cell lung cancer (NSCLC)

Start Date01 Dec 1999

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with Bivatuzumab

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100 Translational Medicine associated with Bivatuzumab

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100 Patents (Medical) associated with Bivatuzumab

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214

Literatures (Medical) associated with Bivatuzumab

01 Sep 2023·Oncology letters

CD44‑hyaluronan axis plays a role in the interactions between colon cancer‑derived extracellular vesicles and human monocytes.

Article

Author: Gałuszka-Bulaga, Adrianna ; Babula, Aneta ; Baj-Krzyworzeka, Monika ; Siedlar, Maciej ; Węglarczyk, Kazimierz

During tumor progression, monocytes circulating in the blood or infiltrating tissue may be exposed to tumor-derived extracellular vesicles (TEVs). The first stage of such interactions involves binding of TEVs to the surface of monocytes, followed by their internalization. The present study examines the role of CD44 molecules in the interactions between monocytes and EVs derived from colon cancer cell lines (HCT116 and SW1116). The efficiency of the attachment and engulfment of TEVs by monocytes is linked to the number of TEVs and time of exposure/interaction. The two investigated TEVs, TEVs_HCT116 and TEVs_SW1116, originating from HCT116 and SW1116 cells, respectively, differ in hyaluronan (HA) cargo, which reflects HA secretion by parental cancer cells. HA-rich TEVs_HCT116 are internalized more effectively in comparison with HA-low TEVs_SW1116. Blocking of CD44 molecules on monocytes by anti-CD44 monoclonal antibody significantly decreased the engulfment of TEVs_HCT116 but not that of TEVs_SW1116 after 30 min contact, suggesting the involvement of the HA-CD44 axis. The three subsets of monocytes, classical, intermediate and non-classical, characterized by gradual changes in the expression of CD14 and CD16 markers, also differ in the expression of CD44. The highest expression of CD44 molecules was observed in the intermediate monocyte subset. Blocking of CD44 molecules decreased the internalization of HA-rich TEVs in all three subsets, which is associated with CD44 expression level. It was hypothesized that HA carried by TEVs, potentially as a component of the 'corona' coating, may facilitate the interaction between subsets of monocytes and TEVs, which may influence the fate of TEVs (such as the rate of TEVs adhesion and engulfment) and change monocyte activity.

01 Jun 2023·Anticancer Research

CD44-positive Cancer Stem-like Cells as a Potential Source of Peritoneal Metastasis After Surgery

Article

Author: Takebayashi, Katsushi ; Shimoji, Miyuki ; Ueki, Tomoyuki ; Kitamura, Mina ; Tani, Masaji ; Sihombing, Andreas Michael ; Kojima, Masatsugu ; Murata, Satoshi ; Tokuda, Aya ; Mekata, Eiji ; Kodama, Hirokazu ; Miyake, Toru ; Kitamura, Naomi

BACKGROUND/AIMThe role of CD44 in gastric cancer-derived peritoneal metastasis is currently unknown. It was previously shown that viable, tumorigenic cancer cells are spilled into the peritoneal cavity during surgery, providing a potential cause of peritoneal recurrence after surgery. The purpose of this study was to elucidate the mechanism of peritoneal metastasis of gastric cancer through the expression of CD44 and to propose a method for preventing peritoneal recurrence.MATERIALS AND METHODSGastric cancer cell line MKN-45 was sorted into CD44+ and CD44- cells and then injected intraperitoneally into NOD/ShiJic-scidJcl mice. Differences in tumor-initiating capacity between the two groups were assessed using in vivo limiting dilution assays. Tumors harvested from both groups were examined for CD44 and ALDH1A1 expression using immunohistochemistry. The effects of CD44 blockade with anti-CD44 antibody on cell invasion and peritoneal metastasis formation in vivo were assessed.RESULTSCD44+ cells showed significantly higher efficiency in initiating peritoneal tumor than CD44- cells. Blockade of CD44 significantly reduced peritoneal dissemination of CD44+ cells in vivo, indicating that the CD44 function of intraperitoneally disseminated cancer cells helped promote the formation of peritoneal metastasis. The margin of established tumors showed clusters of cells co-expressing CD44 and ALDH1A1. Peritoneally administered CD44- cells resulted in peritoneal metastases consisting of CD44+ and CD44- cancer cells.CONCLUSIONCD44 expressing cells are a potential source of peritoneal metastasis after surgery and could be a promising target for preventing peritoneal recurrence.

28 Feb 2023·Blood Advances

EMD originates from hyaluronan-induced homophilic interactions of CD44 variant-expressing MM cells under shear stress

Article

Author: Miwa, Akiyoshi ; Furukawa, Yusuke ; Uchiyama, Michihiro ; Yasui, Hiroshi ; Kuroda, Yoshiaki ; Takeshita, Masataka ; Kodama, Nobuyuki ; Kobayashi, Takahiro ; Bogen, Bjarne ; Kikuchi, Jiro ; Takahashi, Naoto ; Ikeda, Sho ; Osada, Naoki

AbstractExtramedullary disease (EMD) is known to be associated with chemoresistance and poor prognosis in multiple myeloma (MM); however, the mechanisms of its development are not fully understood. Elucidating the mechanism of EMD development and its therapeutic targeting would greatly contribute to further improvement of treatment outcome in patients with MM. Here, we show that bone marrow stroma cell–derived hyaluronan (HA) elicits homophilic interactions of MM cells by binding to surface CD44, especially long-stretch variants, under physiological shear stress and generates cell clusters that might develop into EMD. We recapitulated the development of EMD via administration of HA in a syngeneic murine MM model in a CD44-dependent manner. HA-induced MM cell clusters exhibited the specific resistance to proteasome inhibitors (PIs) in vitro and in murine models via γ-secretase–mediated cleavage of the intracellular domains of CD44, which in turn transactivated PI resistance-inducible genes. Treatment of HA-injected mice with anti-CD44 antibody or γ-secretase inhibitors readily suppressed the development of EMD from transplanted MM cells and significantly prolonged the survival of recipients by overcoming PI resistance. The HA-CD44 axis represents a novel pathway to trigger EMD development and could be a target of the prediction, prevention, and treatment of EMD in patients with MM.

100 Deals associated with Bivatuzumab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Bivatuzumab	-	DB06550

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Mammary adenocarcinoma	Phase 2	-	Boehringer Ingelheim GmbH	01 Jan 2000
Non-Small Cell Lung Cancer	Phase 2	-	Boehringer Ingelheim GmbH	01 Dec 1999
Head and Neck Neoplasms	Phase 2	-	C.H. Boehringer Sohn AG & Co. KG	-