TRION Pharma GmbH

München, Germany

TRION Pharma GmbH

München, Germany

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Eissler N.,Helmholtz Center Munich | Ruf P.,Trion Research GmbH | Mysliwietz J.,Helmholtz Center Munich | Lindhofer H.,Trion Research GmbH | And 2 more authors.
Cancer Research | Year: 2012

A major goal of tumor immunotherapy is the induction of long-lasting systemic T-cell immunity. Bispecific antibodies (bsAbs) that lack the immunoglobulin Fc region confer T-cell-mediated killing of tumor cells but do not induce long-term memory. In contrast, trifunctional bsAbs comprise an appropriate Fc region and, therefore, not only recruit T cells but also accessory cells that bear activating Fcγ receptors (FcγR), providing additional T-cell-activating signals and securing presentation of tumor-derived antigens to T cells. In this study, we show that trifunctional bsAbs induce a polyvalent T-cell response and, therefore, a vaccination effect. Mice were treated with melanoma cells and with a trifunctional bsAb directed against the melanoma target antigen ganglioside GD2 in addition to murine CD3. The trifunctional bsAb activated dendritic cells and induced a systemic immune response that was not replicated by treatment with the F(ab′) 2-counterpart lacking the Fc region. Restimulation of spleen and lymph node cells in vitro yielded T-cell lines that specifically produced interferon-γ in response to tumor. In addition, trifunctional bsAb-induced T cells recognized various specific peptides derived from melanoma-associated antigens. Moreover, these polyvalent responses proved to be tumor-suppressive and could not be induced by the corresponding bsF(ab′)2- fragment. Taken together, our findings provide preclinical proof of concept that trifunctional bsAbs can induce tumor-specific T cells with defined antigen specificity. ©2012 AACR.


Seimetz D.,Fresenius Biotech GmbH | Lindhofer H.,TRION Pharma GmbH | Bokemeyer C.,University of Hamburg
Cancer Treatment Reviews | Year: 2010

Catumaxomab is a trifunctional antibody (trAb) characterized by its unique ability to bind three different cell types: tumor cells, T-cells, and accessory cells. It has two different antigen-binding specificities: one for epithelial cell adhesion molecule (EpCAM) on tumor cells and one for the CD3 antigen on T-cells. Catumaxomab also binds to type I, IIa, and III Fcγ receptors (FcγR) on accessory cells, e.g. macrophages, dendritic cells, and natural killer cells, via its intact Fc region. Its anti-tumor activity results from T-cell-mediated lysis, antibody-dependent cell-mediated cytotoxicity, and phagocytosis via activation of FcγR-positive accessory cells. Importantly, no additional activation of immune cells is necessary for effective tumor eradication by catumaxomab, which represents a self-supporting system. Catumaxomab's efficacy and safety have been demonstrated in a pivotal phase II/III study and supporting phase I/II studies. It is administered as four intraperitoneal (i.p.) infusions on days 0, 3, 7, and 10 at doses of 10, 20, 50, and 150μg, respectively. Catumaxomab has been approved in the European Union since April 2009 for the i.p. treatment of malignant ascites (MA) in patients with EpCAM-positive carcinomas where standard therapy is not available or no longer feasible. Catumaxomab is the first trAb and the first drug worldwide to be approved specifically for the treatment of MA. It is in clinical trials in a number of other indications including ovarian and gastric cancer. Alternative routes of administration are also under evaluation to further exploit the therapeutic potential of catumaxomab in EpCAM-positive carcinomas. © 2010 Elsevier Ltd.


The present invention refers to a method for predicting an improved therapeutic benefit for an individual suffering from a tumor carrying a known tumor-associated cell surface antigen (such as EpCAM). The present invention further refers to a method for the induction of secondary humoral immune responses directed against a second tumor-associated antigen (e.g., another tumor-associated antigen, like HER2/neu) different from the first tumor-associated antigen in an individual suffering from a tumor comprising tumor cells expressing the first tumor-associated antigen, e.g., EpCAM.)


Use of a trifunctional bispecific antibody having the following properties of: a) binding to a T cell; b) binding to EpCAM as tumor-associated antigen on a tumor cell wherein the tumor cell additionally carries the membrane bound glycoprotein CD133; c) binding by its Fc portion to Fc receptor-positive cells for the preparation of a pharmaceutical composition for the destruction of cancer stem cells carrying the tumor-associated antigen EpCAM and the membrane bound glycoprotein CD133 in a population of patients suffering from a tumor.


Patent
Trion Pharma Gmbh | Date: 2012-10-04

The invention relates to a method performed ex vivo for removal of tumor cells from intraoperatively collected blood salvage, to antibodies and scaffold proteins which mimic antibodies for use in said ex vivo method, to the use of said ex vivo method for removal of tumor cells from intraoperatively collected blood salvage followed by reintroducing the so obtained purified blood salvage or of concentrates of erythrocytes purified by said method to a patient from whom said intra-operatively collected blood was obtained, as well as to blood salvage or a concentrate of erythrocytes, both obtainable by said method for reinfusion to said patient.


The invention describes the use of a pharmaceutical preparation containing a trifunctional bispecific and/or trispecific having the following properties:


The present invention describes the use of trifunctional bispecific antibodies for the preparation of a pharmaceutical composition for the prophylaxis and treatment of tumor diseases. It has been found that said trifunctional bispecific antibodies are binding to tumor-associated antigens selected from Her2/neu, CD20, EpCAM, G250, proteoglycans, GD3, GD2, MHC II, EGF-R and CEA, wherein said tumor-associated antigens are expressed on said tumor cell with a low to medium expression level only.


Patent
Trion Pharma Gmbh | Date: 2013-04-10

The invention relates to a method performed ex vivo for removal of tumor cells from intraoperatively collected blood salvage, to antibodies and scaffold proteins which mimic antibodies for use in said ex vivo method, to the use of said ex vivo method for removal of tumor cells from intraoperatively collected blood salvage followed by reintroducing the so obtained purified blood salvage or of concentrates of erythrocytes purified by said method to a patient from whom said intraoperatively collected blood was obtained, as well as to blood salvage or a concentrate of erythrocytes, both obtainable by said method for reinfusion to said patient.


Use of a trifunctional bispecific antibody having the following properties of a) binding to a T cell; b) binding to EpCAM as tumor-associated antigen on a tumor cell wherein the tumor cell additionally carries the membrane bound glycoprotein CD 133; c) binding by its Fc portion to Fc receptor-positive cells for the preparation of a pharmaceutical composition for the destruction of cancer stem cells carrying the tumor-associated antigen EpCAM and the membrane bound glycoprotein CD 133 in a population of patients suffering from a tumor.


The present invention describes the use of trifunctional bispecific antibodies for the preparation of a pharmaceutical composition for the prophylaxis and treatment of tumor diseases. It has been found that said trifunctional bispecific antibodies are binding to tumor-associated antigens selected from Her2/neu, CD20, EpCAM, G250, proteoglycans, GD3, GD2, MHC II, EGF-R and CEA, wherein said tumor-associated antigens are expressed on said tumor cell with a low to medium expression level only.

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