CD40 inhibitors(Tumor necrosis factor receptor superfamily member 5 inhibitors), EpCAM inhibitors(Epithelial cell adhesion molecule inhibitors), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects)

+ [1]

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Neoplasms

Originator Organization

Alligator Bioscience AB

Active Organization-

Inactive Organization

Alligator Bioscience AB

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with CD40/EpCAM bispecific antibody(Alligator Bioscience AB)

100 Translational Medicine associated with CD40/EpCAM bispecific antibody(Alligator Bioscience AB)

100 Patents (Medical) associated with CD40/EpCAM bispecific antibody(Alligator Bioscience AB)

Literatures (Medical) associated with CD40/EpCAM bispecific antibody(Alligator Bioscience AB)

01 Jan 2016·American Journal of Obstetrics and GynecologyQ1 · MEDICINE

Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE), is highly active against primary uterine serous papillary carcinoma cell lines in vitro

Q1 · MEDICINE

Article

Author: Black, Jonathan ; Schwab, Carlton L ; English, Diana P ; Santin, Alessandro D ; Bellone, Stefania ; Azodi, Masoud ; Silasi, Dan-Arin ; Bonazzoli, Elena ; Lopez, Salvatore ; Schwartz, Peter E ; Ratner, Elena ; Cocco, Emiliano ; Predolini, Federica ; Ferrari, Francesca

BACKGROUNDUterine serous carcinoma is an aggressive form of endometrial cancer that carries an extremely poor prognosis. Solitomab is a novel bispecific single-chain antibody construct that targets epithelial cell adhesion molecule on tumor cells and also contains a CD3 binding region. We evaluated the expression levels of epithelial cell adhesion molecule and the in vitro activity of solitomab against primary uterine serous carcinoma cell lines in vitro and ex-vivo in the ascites of patients with uterine serous carcinoma.OBJECTIVEThe purpose of this study was to determine the frequency of expression of epithelial cell adhesion molecule on uterine serous carcinoma cell lines and the ability of solitomab to modulate immune responses (T-cell proliferation, activation, cytokine production, and tumor killing) to tumor cells when it is combined with lymphocytes and epithelial cell adhesion molecule-positive cell lines or epithelial cell adhesion molecule-positive ascitic fluid in vitro.STUDY DESIGNEpithelial cell adhesion molecule expression was evaluated by flow cytometry in a total of 14 primary uterine serous carcinoma cell lines. Sensitivity to solitomab-dependent cellular-cytotoxicity was tested against a panel of primary uterine serous carcinoma cell lines that express different levels of epithelial cell adhesion molecule in standard 4-hour chromium release assays. The proliferative activity, activation, cytokine secretion (ie, type I vs type II), and cytotoxicity of solitomab in autologous tumor-associated T cells in the ascitic fluid of patients with uterine serous carcinoma was also evaluated by carboxyfluorescein succinimidyl ester and flow-cytometry assays. Differences in epithelial cell adhesion molecule expression, solitomab-dependent cellular-cytotoxicity levels were analyzed with the use of an unpaired t test. T-cell activation marker increase and cytokine release were analyzed by a paired t test.RESULTSSurface expression of epithelial cell adhesion molecule was found in 85.7% (12 of 14) of the uterine serous carcinoma cell lines that were tested by flow cytometry. Epithelial cell adhesion molecule-positive cell lines were found resistant to natural killer cells or T-cell-mediated killing after exposure to peripheral blood lymphocytes in 4-hour chromium-release assays (mean killing ± standard of the mean, 2.7% ± 3.1% after incubation of epithelial cell adhesion molecule-positive cell lines with control bispecific antibody construct). In contrast, after incubation with solitomab, epithelial cell adhesion molecule-positive uterine serous carcinoma cells became highly sensitive to T-cell cytotoxicity (mean killing, 25.7% ± 4.5%; P < .0001) by peripheral blood lymphocytes. Ex vivo incubation of autologous tumor-associated lymphocytes with epithelial cell adhesion molecule that expressed malignant cells in ascites with solitomab resulted in a significant increase in T-cell proliferation in both CD4+ and CD8+ T cells, increase in T-cell activation markers (ie, CD25 and HLA-DR), and a reduction in number of viable uterine serous carcinoma cells in ascites (P < .001).CONCLUSIONSolitomab induces robust immunologic responses in vitro that result in increased T-cell activation, proliferation, production of cytokines, and direct killing of tumor cells. These findings suggest that solitomab may represent a novel, potentially effective agent for the treatment of recurrent/metastatic and/or chemo-resistant uterine serous carcinoma-overexpressing epithelial cell adhesion molecule.

01 Jan 2011·mAbsQ2 · MEDICINE

Concentrations of EpCAM ectodomain as found in sera of cancer patients do not significantly impact redirected lysis and T-cell activation by EpCAM/CD3-bispecific BiTE antibody MT110

Q2 · MEDICINE

Article

Author: Patrick A. Baeuerle ; Sandra Lippold ; Sabine Denzel ; Silke Petsch ; Dominik Rüttinger ; Andreas Wolf ; Olivier Gires

Ectodomains of target antigens for antibody-based therapies can be shed from the target cell surface and found in sera of patients. Shed ectodomains of therapeutic targets not only pose the risk of sequestering therapeutic antibodies but, in a multimeric form, of triggering T cell activation by bispecific antibodies binding to CD3 on T cells. Recently, epithelial cell adhesion molecule (EpCAM) has been shown to be activated by release of its ectodomain, called EpEX. Here, we show that only very low amounts of EpEX are detectable in sera of cancer patients. Among 100 cancer patient samples tested, only 17 (17%) showed serum levels of EpEX in excess of 0.05 ng/ml with highest EpEX concentrations of 5.29, 1.37 and 0.52 ng/ml. A recombinant form of human EpEX (recEpEX) was produced to assess its possible effect on redirected lysis and T cell activation by EpCAM/CD3-bispecific BiTE antibody MT110, currently being tested in patients with solid tumor malignancies. RecEpEX had a very minor effect on redirected lysis by MT110 with an approximate IC 50 value of 3,000 ng/ml, which is a concentration close to three orders of magnitude higher than the highest EpEX concentration found in cancer patients. Concentrations of 30 ng/ml EpEX in combination with 250 ng/ml MT110 were minimally required to induce a detectable activation of CD4 (+) and CD8 (+) T cells. We conclude that soluble EpEX in sera of cancer patients is unlikely to pose an issue for the efficacy or safety of MT110, and perhaps other antibodies binding to N-terminal epitopes of EpCAM.

100 Deals associated with CD40/EpCAM bispecific antibody(Alligator Bioscience AB)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	SE	Alligator Bioscience AB	15 Sep 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

CD40/EpCAM bispecific antibody(Alligator Bioscience AB)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation