Catumaxomab – trifunctional anti-EpCAM antibody used to treat malignant ascites

Bokemeyer, Carsten

doi:10.1517/14712598.2010.504706

Cited by 45 publications

(30 citation statements)

References 34 publications

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“…3,38,40,[72][73][74][75] The circular self-contained CODV architecture with its voluminous Fab region could raise the concern that binding of FcRs or hexamerization which potentiates complement activation might be perturbed. 40,51,76 Also, both, binding of surface antigens on target cells with concomitant FcgR engagement on immune effector cells and assembly of the complement components on antigen-bound CODV-Ig are subjected to 3D constraints that one might imagine incompatible with CODV architecture.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Two bispecific antibody therapeutics, catumaxomab (Removab Ò ) and blinatumomab (Blincyto Ò ), have been approved, and over ten bispecific antibodies are currently in clinical development for treatment of inflammatory diseases, hemophilia A, or cancers. 3,4 The drug-like properties of bispecific biotherapeutics described in the literature vary widely. Molecular weights range from »55 kDa to over 300 kDa, their valences for antigen binding are from two to six, and serum half-lives are reported to be between »0.5 hours and »2 weeks.…”

Section: Introductionmentioning

confidence: 99%

“…[30][31][32][33][34][35] Furthermore, they may elicit antibody-dependent cell-mediated cytotoxicity or phagocytosis (ADCC or ADCP, respectively) via Fcg receptors (FcgRs), which is important for cancer biotherapeutics. 3,[36][37][38][39] Fully functional Fc domains may also confer the potential to trigger the classical pathway of complementdependent humoral response, and thereby elicit complementdependent cytotoxicity (CDC). 40,41 To overcome major limitations of existing bispecific biotherapeutics and to create a universally applicable format that can be fine-tuned in multiparametric drug optimization, we designed the CODV format to serve as a versatile platform for the development of bispecific agents.…”

Section: Introductionmentioning

confidence: 99%

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CODV-Ig, a universal bispecific tetravalent and multifunctional immunoglobulin format for medical applications

Steinmetz

Vallée

Beil

et al. 2016

mAbs

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Bispecific immunoglobulins (Igs) typically contain at least two distinct variable domains (Fv) that bind to two different target proteins. They are conceived to facilitate clinical development of biotherapeutic agents for diseases where improved clinical outcome is obtained or expected by combination therapy compared to treatment by single agents. Almost all existing formats are linear in their concept and differ widely in drug-like and manufacture-related properties. To overcome their major limitations, we designed cross-over dual variable Ig-like proteins (CODV-Ig). Their design is akin to the design of circularly closed repeat architectures. Indeed, initial results showed that the traditional approach of utilizing (G4S) x linkers for biotherapeutics design does not identify functional CODV-Igs. Therefore, we applied an unprecedented molecular modeling strategy for linker design that consistently results in CODV-Igs with excellent biochemical and biophysical properties. CODV architecture results in a circular self-contained structure functioning as a self-supporting truss that maintains the parental antibody affinities for both antigens without positional effects. The format is universally suitable for therapeutic applications targeting both circulating and membrane-localized proteins. Due to the full functionality of the Fc domains, serum half-life extension as well as antibody-or complement-dependent cytotoxicity may support biological efficiency of CODV-Igs. We show that judicious choice in combination of epitopes and paratope orientations of bispecific biotherapeutics is anticipated to be critical for clinical outcome. Uniting the major advantages of alternative bispecific biotherapeutics, CODV-Igs are applicable in a wide range of disease areas for fast-track multi-parametric drug optimization.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CODV-Ig, a universal bispecific tetravalent and multifunctional immunoglobulin format for medical applications

Steinmetz

Vallée

Beil

et al. 2016

mAbs

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“…In particular, since anti-EpCAM target therapy are available [25], it could be of interest to identify patients with EpCAM-positive MPs to define more personalized therapeutic approaches [26].…”

Section: Discussionmentioning

confidence: 99%

False Negative Pleural Cytology in Patient with Malignant Pleurisies: Is Pleural EpCAM-Positive Microparticles a Complementary Tool for Diagnosis?

Roca¹,

Laroumagne²,

Lacroix³

et al. 2017

J Mol Biomark Diagn

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The diagnosis of neoplastic pleurisies remains difficult because of frequent false negative cytological analysis. Thoracoscopy remains the gold standard to distinguish benign from malignant pleural effusion, but it is invasive and not suitable for all patients.Microparticles (MPs) are promising potential biomarkers and could represent a new approach to identify patients with malignant pleural effusions.We have recently reported the presence of EpCAM-positive-MPs (EpCAM+MPs) in malignant pleurisies that could be routinely used as a complementary tool with cytology for the diagnosis of pleural malignancy.Here we describe three cases of pleural cancer patients negative for cancer cells but positive for EpCAM+MPs in the pleural fluid.This study confirmed the possibility to apply in clinical practice recent data about EpCAM+MPs, detected in pleural fluid, as a non-invasive pleural biomarker useful to increase sensitivity of cytology. In particular, we suggest in patients with a strong suspicion of pleural cancer to search pleural EpCAM+-MPs as a complementary diagnostic tool in case of negative cytological analysis of pleural fluid.

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“…Catumaxomab is a trifunctional bispecifi c antibody that binds to tumour cells expressing human epithelial cell adhesion molecule (EpCAM), known to be expressed in gastric, hepatobiliary, colonic, and other epithelial carcinomas [17]) and redirects CD3+ T lymphocytes and Fcγ-receptor-positive accessory tumour cells such as macrophages, dendritic cells and natural killer cells to malignant cells [21]. Based on preclinical data simultaneous activation of T cells and accessory immune cells induces a variety of immunological events that ultimately lead to tumour cell elimination by diff erent killing mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), phagocytosis and perforine-dependent lysis [22,23].…”

Section: Intraperitoneal Monoclonal Antibodiesmentioning

confidence: 99%

Malignant ascites – current treatment and novel therapeutic options

Stange

2012

memo

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Malignant ascites is a common problem in patients with advanced malignancies and peritoneal spread of tumour. Treatment strategies include paracentesis, diuretics and peritoneovenous shunts; however, there are no established evidence-based guidelines for optimal therapy. Th is review is intended to add clarity to the current procedures for the management of malignant ascites, and furthermore discusses new promising approaches.

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Catumaxomab – trifunctional anti-EpCAM antibody used to treat malignant ascites

Cited by 45 publications

References 34 publications

CODV-Ig, a universal bispecific tetravalent and multifunctional immunoglobulin format for medical applications

CODV-Ig, a universal bispecific tetravalent and multifunctional immunoglobulin format for medical applications

False Negative Pleural Cytology in Patient with Malignant Pleurisies: Is Pleural EpCAM-Positive Microparticles a Complementary Tool for Diagnosis?

Malignant ascites – current treatment and novel therapeutic options

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