Jerusalem, Israel
Jerusalem, Israel

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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.


Aronin A.,Hebrew University of Jerusalem | Amsili S.,KAHR medical | Prigozhina T.B.,Hebrew University of Jerusalem | Tzdaka K.,Hebrew University of Jerusalem | And 4 more authors.
PLoS ONE | Year: 2013

Background:New strategies for the treatment of hepatocellular carcinoma (HCC) are needed, given that currently available chemotherapeutics are inefficient. Since tumor growth reflects the net balance between pro-proliferative and death signaling, agents shifting the equilibrium toward the latter are of considerable interest. The TWEAK:Fn14 signaling axis promotes tumor cell proliferation and tumor angiogenesis, while TRAIL:TRAIL-receptor (TRAIL-R) interactions selectively induce apoptosis in malignant cells. Fn14•TRAIL, a fusion protein bridging these two pathways, has the potential to inhibit tumor growth, by interfering with TWEAK:Fn14 signaling, while at the same time enforcing TRAIL:TRAIL-R-mediated apoptosis. Consequently, Fn14•TRAIL's capacity to inhibit HCC growth was tested.Results:Fn14•TRAIL induced robust apoptosis of multiple HCC cell lines, while sparing non-malignant hepatocyte cell lines. Differential susceptibility to this agent did not correlate with expression levels of TRAIL, TRAIL-R, TWEAK and Fn14 by these lines. Fn14•TRAIL was more potent than soluble TRAIL, soluble Fn14, or a combination of the two. The requirement of both of Fn14•TRAIL's molecular domains for function was established using blocking antibodies directed against each of them. Subcutaneous injection of Fn14•TRAIL abrogated HCC growth in a xenograft model, and was well tolerated by the mice.Conclusions:In this study, Fn14•TRAIL, a multifunctional fusion protein originally designed to treat autoimmunity, was shown to inhibit the growth of HCC, both in vitro and in vivo. The demonstration of this fusion protein's potent anti-tumor activity suggests that simultaneous targeting of two signaling axes by a single fusion can serve as a basis for highly effective anti-cancer therapies. © 2013 Aronin et al.


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.


Patent
KAHR medical and HADASIT MEDICAL RESEARCH SERVICE AND DEVELOPMENT Co. | Date: 2016-06-09

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.


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.


KAHR medical | Entity website

OverviewKAHR Medical ("KAHR") is pioneering the development of "third generation biological drugs," a unique class of proprietary fusion-protein molecules with clear and far-reaching advantages. KAHR's technology represents a paradigm shift in protein-based pharmaceuticals that will significantly expand available treatment options for cancer and autoimmune disorders ...


KAHR medical | Entity website

Development Pipeline DSP molecules represent a novel class of biological drugs and KAHR is the first company to develop DSP-based therapeutics Several DSP molecules have been intensely studied in the last decade, mostly by research teams at the University of Pennsylvania and the Hadassah Medical Center (Israel), and their promise as drug candidates has been documented in multiple scientific publications. KAHR has selected twoDSP molecules that have shown significant in-vitro and in-vivo efficacy as its current drug development pipeline -1 ...


KAHR medical | Entity website

Investors The company In February2016, KAHR completed its Series-B financing, raising a total of $15M The company is based in Israel KAHR is the first company to develop DSP-based therapeutics The company's scientific development is supported by an exceptional Scientific and Clinical Advisory BoardIntellectual Property KAHR has a worldwide exclusive license from the University of Pennsylvania for the DSP technology IP portfolio, protecting its main products KAHR submitted three new DSP-based patents, two of theapplications are protecting novel DSP-basedplatforms; DSP-Hexamers and DSP-Clusters, each covering hundreds of drug candidatesDSP platform technology First-in-Class: Fusion proteins with two functional sides. Novel mode-of-action based on unique molecular structures Multiple clinical applications (e ...


KAHR medical | Entity website

In the New September 11, 2013: KAHR Medical raises $2.35M from Thomas Elderad, Sanofi and Hadasit BioJune 25, 2012: KAHR Medical raises $2 ...


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