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Jerusalem, Israel

Orbach A.,Hebrew University of Jerusalem | Rachmilewitz J.,Hebrew University of Jerusalem | Shani N.,KAHR medical | Isenberg Y.,Hebrew University of Jerusalem | And 4 more authors.
American Journal of Pathology | Year: 2010

Evolution of apoptosis resistance in both lymphoma and leukemia cells is well documented, and induction of apoptosis in malignant cells is a major goal of cancer therapy. Up-regulation of anti-apoptotic signals is one of the mechanisms whereby resistance to apoptosis emerges. We have previously described the fusion proteins CD40·FasL and CTLA-4·FasL, which are formed from two functional membrane proteins and induce apoptosis of activated T cells. The present study explores the potential use of CD40·FasL and CTLA-4·FasL for the killing of malignant cells of lymphatic origin. Using malignant B and T cell lines that differ in surface expression of costimulatory molecules, we found that CTLA-4·FasL induces effective apoptosis of cells expressing CD95 and activates caspases 3, 8, and 9. Only B7-expressing B cells responded to CTLA-4·FasL with rapid abrogation of cFLIP expression. CD40·FasL effectively killed only the T cells that express high levels of CD40L in addition to CD95. In these cells, CD40·FasL significantly diminished cFLIP expression. Importantly, each of the fusion proteins is more potent than its respective components parts, alone or in combination. Thus, the proteins with their two functional ends deliver a pro-apoptotic signal and, in parallel, inhibit an anti-apoptotic signal, thus optimizing the wanted, death-inducing effect. Therefore, these proteins emerge as promising agents to be used for targeted and specific tumor cell killing. Copyright © American Society for Investigative Pathology. Source


A stable fusion protein, wherein in solution, a majority of the fusion proteins are in the homo-hexamer form, which may be prepared for example as a CTLA4-FasL fusion protein.


Patent
Hadasit Medical Research Service And Development Co Ltd and KAHR medical | Date: 2011-09-28

Use of a chimeric protein selected from the group consisting of CTLA4-FasL and CD40-FasL proteins for treatment of lymphoma and/or a multiple myeloma and/or a leukemia as described herein, and pharmaceutical compositions and methods of treatment thereof.


KAHR medical | Entity website

KAHR-102 KAHR-102 is expected to initiate clinical trials in early2016.Mode of action KAHR-102 is a fusion protein that links portions of two immune and cancer-related membrane proteins; CTLA-4 and FasL ...

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