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1662
Immunotherapy, that is the use of the immune system to treat cancer, is currently a leading candidate in the combat against cancer. Unlike the toxic effects of both chemotherapy and radiation, immunotherapy is considered to have mild side effects due to its ability to differentiate between healthy and...

Immunotherapy, that is the use of the immune system to treat cancer, is currently a leading candidate in the combat against cancer. Unlike the toxic effects of both chemotherapy and radiation, immunotherapy is considered to have mild side effects due to its ability to differentiate between healthy and cancerous cells. Also, the therapeutic role of the immune system is an essential element in the healing process due to bone marrow transplantation for hematologic malignancies.
However, a more efficacious and less toxic T cells based treatment is required. Effective therapy depends on the functional avidity between T cell receptors (TCRs) and peptide-MHC complex (pMHC). However the natural affinity of TCR is low and they do not naturally undergo the processes that improve antibody affinity, such as somatic hypermutation (SHM). Currently there is no method of increasing the affinity of a TCR to its ligand. Moreover there is no knowledge on how use affinity maturated TCRs for creating anti-tumor reactive cells
This technology presents a method of increasing the affinity of a TCR to its ligand. This is done by subjecting TCR genes to SHM via the enzyme Activation Induced cytidine Deaminase (AID). The technology further provides affinity maturated TCRs (in cell- bound or in soluble form) and their pharmaceutical potential for immunotherapy. 

Applications


  • Generating anti-tumor T cells
  • Generating T cells reactive against selected antigen

Advantages


  • Rapid
  • Effective

Technology's Essence


This novel technology reveals that the affinity of a TCR to its ligand may be increased remarkably by subjecting TCR genes to SHM, directed by AID.
First a nucleic acid construct encoding a TCR gene is expressed in a host cell. Next SHM is used to introduce mutations to the TCR gene. Last, the the cells will be analyzed for affinity maturation by tetramer staining and subsequently sorted by FACS.
There are three parallel approaches to perform affinity maturation for the TCR: (1) Ex-vivo affinity maturation system, using Tet-regulated expression of AID (2) Ex-vivo affinity maturation system, using controlled expression of AID by mRNA electrophoresis (3) In-vitro affinity maturation system, using extracts from cells that are in SHM and recombinant AID.

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  • Prof. Rachel Lea Eisenbach
1621
Novel treatment for angiogenesis-related diseases.Angiogenesis — the growth of new blood vessels from pre-existing vasculature — has an essential role in development, reproduction and repair. Pathological angiogenesis is a common theme in a broad range of diseases such as cancer, autoimmune diseases,...

Novel treatment for angiogenesis-related diseases.Angiogenesis — the growth of new blood vessels from pre-existing vasculature — has an essential role in development, reproduction and repair. Pathological angiogenesis is a common theme in a broad range of diseases such as cancer, autoimmune diseases, age-related macular degeneration and atherosclerosis. The global market for angiogenesis stimulators and inhibitors is forecast to reach ~US $50 billion by the year 2015. Most of the currently marketed angiogenesis regulators, such as Avastin, typically display modest efficacy and therefore further highlight the great need for the development of novel therapeutics. The current technology presents a novel method to treat angiogenesis-related disorders by modulating apolipoprotein B (ApoB).

Applications


  • ApoB is a potential therapeutic target for the treatment of cancer and other non-neoplastic diseases.
  • ApoB levels may serve as a biomarker for cancer metastasis.

Advantages


  • The anti-angiogenic effect of LDL administration was demonstrated in vivo, in zebrafish models, as well as in vitro, in relevant human cells lines.
  • Regulation of ApoB levels may be applied to treat a broad range of angiogenesis-dependent diseases.
  • Detection of ApoB levels can be readily achieved by analysis of body fluids such as blood and plasma.

Technology's Essence


Using a high-throughput genetic screen for vascular defects in zebrafish, researchers at the Weizmann Institute of Science have identified a genetic mutation that leads to excessive angiogenesis. The mutated gene is responsible for the assembly of ApoB-containing lipoproteins such as LDL, otherwise known as the ‘bad’ cholesterol. The group has found that low levels of LDL promote the formation of new blood vessels by directly interacting with the VEGF pathway. The outlined technology offers methods to modulate the levels of ApoB in order to stimulate, or inhibit angiogenesis, dependent on the therapeutic strategy. For example, inhibition of angiogenesis by increasing ApoB levels may repress tumor growth and attenuate its metastatic potential. In another application of this technology, increased circulating levels of ApoB can serve as a biomarker for the overproduction of blood vessels, thus enabling early diagnosis of pathogenic states in angiogenesis-dependent diseases.

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  • Prof. Karina Yaniv
1629
A new unsupervised learning tool for analyzing large datasets using very limited known data via clustering was developed by the group of Prof. Domany. This solution was originally demonstrated for inferring pathway deregulation scores for specific tumor samples on the basis of expression data.Nearly...

A new unsupervised learning tool for analyzing large datasets using very limited known data via clustering was developed by the group of Prof. Domany. This solution was originally demonstrated for inferring pathway deregulation scores for specific tumor samples on the basis of expression data.
Nearly all methods analyze pathway activity in a global “atomistic” manner, based on an entire sample set, not attempting to characterize individual tumors. Other methods use detailed pathway activity mechanism information and other data that is unavailable in a vast majority of cancer datasets.
The new algorithm described here transforms gene-level information into pathway- level information, generating a compact and biologically relevant representation of each sample. This can be used as an effective prognostic and predictive tool that helps healthcare providers to find optimal treatment strategies for cancer patients. Furthermore, this method can be generically used for reducing the degrees of freedom in order to derive meaningful output from multi-dimensional data using limited knowns.

Applications


  • Personalized cancer treatment.
  • A tool for mining insight from large datasets with limited knowns.

Advantages


  • Provides personalized solutions.
  • Can be utilized for rare conditions with very limited known information.
  • Proved on real oncologic datasets.
  • A Generic unsupervised learning tool.

Technology's Essence


The algorithm analyzes NP pathways, one at a time, assigning a score DP(i) to each sample i and pathway P, which estimates the extent to which the behavior of pathway P deviates from normal, in sample i. To determine this pathway deregulation score the expression levels of those dP genes that belong to P using available databases are used. Each sample i is a point in this dP dimensional space; the entire set of samples forms a cloud of points, and the “principal curve” that captures the variation of this cloud is calculated. Then each sample is projected onto this curve. The pathway deregulation score is defined as the distance DP(i), measured along the curve, of the projection of sample i, from the projection of the normal samples.

 

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  • Prof. Eytan Domany
  • Prof. Eytan Domany
1555
Albumin binding probe for extending the lifetime of drugs. Most polypeptide drugs, in particular non-glycosylated proteins of molecular mass less than 50 kDa, are short-lived species in vivo having circulatory half lives of 5-20 min. Drug association with endogenous albumin may be suitable for...

Albumin binding probe for extending the lifetime of drugs. Most polypeptide drugs, in particular non-glycosylated proteins of molecular mass less than 50 kDa, are short-lived species in vivo having circulatory half lives of 5-20 min. Drug association with endogenous albumin may be suitable for designing an approach to protract the action in vivo of, potentially, any short-lived peptide/protein drug. In doing so two principal obstacles must be overcome: (1) following its conjugation, the probe introduced into a peptide or a protein should have sufficient affinity to albumin to manifest prolonged action in vivo, and (2) in case such covalent introduction results in an inactive product, the latter should be capable to undergo slow reactivation at physiological conditions. The present invention relates to engineering prolonged-acting prodrugs employing an albumin-binding probe that undergoes slow hydrolysis at physiological conditions.

Applications


  • Prolonging half life of short-lined drugs

Advantages


  • Prolonging the action of the drug without effecting its activity 
  • A desirable pharmacokinetic pattern

Technology's Essence


Since albumin is long-lived in vivo, drugs and endogenous substances that tightly associate with it have lower clearance rates than that of the unbound substances, and exhibit prolonged lifetime profiles in vivo. The present invention is based on a concept according to which a long chain fatty acid (LCFA) like albuminbinding compound is covalently linked to a short-lived amino-containing drug to form a non-covalent drug conjugate capable of associating with albumin in vivo, i.e., a long-lived prodrug that gradually releases the pharmacologically active constituent. This approach has been successfully implemented with several drugs (e.g. insulin, exendin and gentamicin).

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  • Prof. Matityahu Fridkin
  • Prof. Yoram Shechter
1640
Although early programs targeting MMPs (matrix metalloproteins) were largely unsuccessful due to adverse side effects, they remain a viable and highly desirable therapeutic target. The main obstacle in the attempts to target MMPs is the ability to selectively target individual family members. The...

Although early programs targeting MMPs (matrix metalloproteins) were largely unsuccessful due to adverse side effects, they remain a viable and highly desirable therapeutic target. The main obstacle in the attempts to target MMPs is the ability to selectively target individual family members. The present invention provides highly selective targeted therapy against MMP-7, which is strongly associated with aspects of cancer development such as angiogenesis and metastasis.
The innovative concept leading to this high selectivity is immunization with both a synthetic metal-protein mimicry molecule, previously developed by the present inventors, followed by the metalloenzyme itself (e.g. MMP-7). The resulting antibody exhibits exceptional degree of specificity towards MMP-7 over other MMPs.
The present technology offers an opportunity to re-introduce improved MMP-targeting agents to the cancer therapeutics market, in particular aggressive cancers that face a major unmet medical need. 

Applications


  • Therapy for MMP-7 associated diseases
  • Diagnostic tool for MMP-7 associated diseases

Advantages


  • Highly selective
  • Safe – avoids adverse effects that are associated with broad spectrum MMP inhibitors.
  • Efficient – targeting a physiological active conformation of the enzyme

Technology's Essence


The present technology is based on a previous invention that was developed in Prof. Sagi's lab, of synthetic metal-protein mimicry molecules that mimic the conserved structure of the metalloenzyme catalytic zinc-histidine complex within the active site of each MMP enzyme.
These molecules were shown to be powerful immunogens in the generation of highly selective MMP antibodies since they recognize both electrical and structural determinants residing within the enzyme active site. The potential of this method to successfully generate MMP-targeting therapeutics was shown for MMP-9/2 inhibitory antibodies in mouse models of inflammatory bowel disease.
Prof Sagi and her team now take this invention a step further to achieve even higher specificity. They show that immunizing with the mimicking molecules described above, followed by immunization with the metalloenzyme itself increases selectivity further.   
Implemented for MMP-7-targeting, this approach yielded an antibody with a 5 fold lower Ki towards MMP-7 than towards other MMPs (e.g. MMp-2 and MMP-9).


 

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  • Prof. Irit Sagi
  • Prof. Irit Sagi
1602
A novel technology for robust downregulation of bacterial genes.RNAi (RNA interference) is a powerful method for downregulation of gene expression in eukaryotic systems. RNAi-based technologies are extensively applied as scientific research tools, as well as actively explored as promising therapeutic...

A novel technology for robust downregulation of bacterial genes.RNAi (RNA interference) is a powerful method for downregulation of gene expression in eukaryotic systems. RNAi-based technologies are extensively applied as scientific research tools, as well as actively explored as promising therapeutic agents. However, although an efficient way to dowregulate bacterial and microbial gene expression has been long sought after, RNAi is not applicable in these species. The present technology offers a rapid and simple means to silence gene products in prokaryotic systems.

Applications


  • Treatment of bacterial infection, by targeting bacterial genes vital for antibiotic resistance or bacterial virulence.
  • Enhanced biofuel production by targeting genes that interfere with ethanol and/or hydrogen biosynthesis.
  • Generation of improved bacterial strains for the diary industry (e.g. phage-resistant strains).
  • Discerning prokaryotic gene function by silencing the expression of the gene product.

Advantages


  • The present technology may offer means to treat antibiotics-resistant strains.
  • Because CRISPR-based technology does not involve ‘classical’ genetic engineering, the resulting products do not require labeling as 'genetically modified'.
  • CRISPR-based technology system allows for the development of a rapid, scalable and high-throughput platform to probe the function of genetic circuits in prokaryotes.

Technology's Essence


CRISPR (clusters of regularly interspaced short palindromic repeats) is a recently discovered anti-viral system that functions as the prokaryotic-equivalent of the adaptive immune system. CRISPR provides bacteria with protection against foreign genetic elements such as viruses by incorporating short stretches of invading DNA sequences in genomic CRISPR loci. These integrated sequences are thought to function as a genetic memory that prevents the host from being infected by the viruses and other genetic elements containing this recognition sequence. A team of researchers at the Weizmann Institute, headed by Dr. Rotem Sorek, has developed a unique technology to gain robust and rapid silencing of prokaryotic gene expression by exploiting the CRISPR system capacity to efficiently downregulate gene products. This potent technology can potentially be utilized in a broad range of areas such as in the agriculture, food and pharmaceutical industries as well as in the scientific research arena.

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  • Prof. Rotem Sorek
1407
Thermotolerant photosynthetic organisms endure worsening climate conditions such as increased temperatures and higher levels of CO2. These novel organisms maintain photosynthetic activity and growth under a wide temperature range (15-45oC) as opposed to their wild-type counterparts. Thermotolerant...

Thermotolerant photosynthetic organisms endure worsening climate conditions such as increased temperatures and higher levels of CO2. These novel organisms maintain photosynthetic activity and growth under a wide temperature range (15-45oC) as opposed to their wild-type counterparts.

Thermotolerant organisms also exhibit higher transparency to light. Photosynthetic efficiency is maintained even though they produce and utilize less chlorophyll molecules; therefore less surface area is required for optimal cultivation. Furthermore, increased CO2 concentrations are preferable for thermotolerant organisms’ efficient photosynthesis.

The innovative solution discovered at The Weizmann Institute, involves replacement of 1-2 amino acid residues in a protein motif within the D1 protein subunit of Photosystem II (the protein complex responsible for the conversion of solar energy to a useful form of energy by photosynthesis). Such a solution has the potential to provide platforms for food production and sustainable energy in regions with harsh climate conditions that until today, were deemed unfit for cultivation.

Applications


  • Bacterial platform to produce biomass or materials (e.g. nutraceuticals) in higher temperatures and higher CO2.
  • Food and biofuel production: adaptation of crops to harsh climates.

Advantages


  • Enhanced Thermal stability and plasticity of the modified organisms to a much broader range than observed for the native organisms.
  • Greater Light penetration (e.g. in ponds) without losing photosynthetic efficiency - thermotolerant organisms maintain efficient activity with less chlorophylls thus allowing greater transmission of light to deeper spaces.
  • Thermotolerant organisms withstand high CO2 concentrations.

Technology's Essence


Professor Avigdor Scherz and his team focused on the sequences of the two major protein subunits D1 and D2 found in all purple bacteria PSII reaction centers. Two sites, D1-209 and D1-212, were found to show consistent changes between mesophilic, thermotolerant and thermophilic organisms including cyanobacteria, algae and green plants.

The sites are positioned in a GXXXG-like structural motif (where G denotes small residues such as Gly, Ala, Ser, Cys and Thr) typical of helix-helix interactions. The motif was found at the points of closest contact between the two major protein subunits, D1 and D2. It was shown that mutations in the amino acids within the identified GXXXG-like motif  result in modification of the local flexibility of the reaction center and, consequently, in the induction of thermophilic behavior.

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  • Prof. Avigdor Scherz
1499
Bladder cancer is a common malignancy; it is the 4th most common cancer in males and the 9th in females.  The presenting symptom is usually blood in the urine, and diagnosis is currently based on cystoscopy, which is invasive, costly, painful and time consuming.  To date, no biomarker has been...

Bladder cancer is a common malignancy; it is the 4th most common cancer in males and the 9th in females.  The presenting symptom is usually blood in the urine, and diagnosis is currently based on cystoscopy, which is invasive, costly, painful and time consuming.  To date, no biomarker has been identified in the urine that might be used for screening, staging, prognosis and monitoring treatment.  We now report that the amount of the 60 kDa heat shock protein (HSP60) in a subject’s urine is a biomarker for muscle invasion in patients with bladder cancer – stage T2 and higher.  Moreover, subjects with stage T1 disease can be stratified by their urine levels of HSP60 into a sub-group likely to progress into stage T2 or into a sub-group more likely to respond to conservative treatment with BCG, which does not require removal of the bladder.  The distinction between these two sub-groups of T1 bladder cancer can identify earlier subjects in need of cystectomy, while sparing others unnecessary major surgery.

Applications


  • Screening subjects with overt hematuria, or at risk of developing bladder cancer (such as heavy smokers)
  • tratifying bladder cancer subjects
  • Prognosis
  • Determining treatment program
  • Monitoring response to therapy.

Advantages


  • Non-invasive
  • Easy to apply
  • Relatively inexpensive
  • Prognositic.

Technology's Essence


Quantitative measurement of HSP60 levels in a subject’s urine by ELISA, radio-immunoassay or other simple assays.

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  • Prof. Irun R. Cohen
1245

Applications


The novel DNA Aptamer is a promising candidate for therapeutic as well as diagnostic uses: Therapeutic: A novel therapy for Influenza Diagnostics: Detection of Influenza infection in vertebrates such as avian, swine and human

Technology's Essence


Scientists at the Weizmann Institute of Science describe a novel oligonucleotide, also known as an Aptamer, which has been designed to complement the receptor-binding region of the influenza haemagglutinin molecule. It was constructed by screening a DNA library and processing by the SELEX procedure. This DNA Aptamer comprises of a polynucleotide sequence that can bind to a polypeptide within the binding region of the influenza virus to the host cell. The proposed mode of action of this Aptamer is by blocking the binding of influenza virus to target cell receptors and consequently preventing the virus invasion into the host cells. Aptamer is capable of inhibiting the haemagglutinin capacity of the virus and the viral infectivity in vitro. Furthermore, it was shown in an animal model to inhibit viral infection by different influenza strains, as manifested by up to 99% reduction of virus burden in the lungs of treated mice.

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  • Prof. Ruth Arnon
1397
A novel antibody which can be used, for the first time, to recognize ubiquitinated histone 2B. This technology is novel in its ability to recognize proteins and their destinations, and may serve in diagnostics and immunoprecipitation processes.

A novel antibody which can be used, for the first time, to recognize ubiquitinated histone 2B. This technology is novel in its ability to recognize proteins and their destinations, and may serve in diagnostics and immunoprecipitation processes.

Applications


Primary applications in research. Use as a detection tool in western blotting, immunoprecipitation and chromatin immunoprecipitation. Might be used for monitoring processes associated with modulations of ubiquitinated-H2B levels.

Technology's Essence


The invention involves the generation of antibodies specific to ubiquitinated-H2B which selectively recognize H2B when it is ubiquitinated but not H2B in its unmodified state, or ubiquitin unconjugated to H2B.

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  • Prof. Moshe Oren
1441
New protein as a target to treat B cell-related cancer.Chronic lymphocytic leukemia (CLL), a malignant disease characterized by the accumulation of B lymphocytes in the blood, lymphoid organs, and bone marrow, is the second most common type of leukemia in adults, accounting for about 7,000 new cases of...

New protein as a target to treat B cell-related cancer.
Chronic lymphocytic leukemia (CLL), a malignant disease characterized by the accumulation of B lymphocytes in the blood, lymphoid organs, and bone marrow, is the second most common type of leukemia in adults, accounting for about 7,000 new cases of leukemia each year. Presently, there is no cure for CLL, and the overall goal of leukemia treatment is to bring about a remission. Therefore, identifying new proteins that may serve as a target for inducing cell death in the malignant cells is highly desirable. The present technology identifies a new regulator protein that is essential for the survival of CLL cells.

Applications


• Treatment of CLL, as well as other B cell-related cancers (e.g. gastric cancer and renal cell carcinoma), by blocking CD84 activity
• Diagnosis of CLL

Advantages


• Very specific to malignant B cells
• Diagnosis, and therefore treatment, can be made at early stages of the disease

 


Technology's Essence


B cells taken from CLL patients have a high level of the protein CD84. Stimulation of CD84 upregulates the survival of B-CLL. However, inhibition of CD84 activity with a blocking antibody downregulates the expression of another protein which controls B-CLL survival, thus inducing cell death. Therefore, the present invention reveals CD84 as a regulator of B-CLL survival

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  • Prof. Idit Shachar
1518
Improved immunotherapy for breast cancer. Monoclonal antibodies (mAbs) to ErbB-2/HER2 growth factor receptor, or to its sibling, the epidermal growth factor receptor (EGFR), prolong survival of cancer patients, especially when combined with cytotoxic therapies. However, low effectiveness of...

Improved immunotherapy for breast cancer.

Monoclonal antibodies (mAbs) to ErbB-2/HER2 growth factor receptor, or to its sibling, the epidermal growth factor receptor (EGFR), prolong survival of cancer patients, especially when combined with cytotoxic therapies. However, low effectiveness of therapeutic mAbs and the evolution of patient resistance call for improvements. Furthermore, the response to the clinically approved monotherapy of Herceptin (a humanized mAb directed against ErbB-2), is relatively low (~15%) and short lived (median duration, 9 months). Therefore, there is a need to improve the therapeutic treatment against this receptor. The present technology enhances the therapeutic activity of anti-ErB-2 receptor antibodies, by combining two or more epitope-distinct antibodies.

Applications


  • Improved treatment of ErbB-2-overexpressing tumors (e.g. in breast and ovary cancers).


Advantages


  • May enhance patient response and delay acquisition of resistance.
  • Enhancement of therapeutic efficacy and synergy with chemotherapy.

Technology's Essence


Optimal selection of mAbs for cancer immunotherapy may improve its therapeutic potential. The outlined technology addresses an emerging strategy, which enhances the therapeutic activity of anti-receptor antibodies by combining two mAbs engaging distinct epitopes. It was demonstrated that pairs of anti-ErbB-2 mAbs better inhibit ErbB-2-overexpressing tumors than the respective individual mAbs, both in vitro and in vivo.

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  • Prof. Yosef Yarden
1033
A novel diagnostic test to identify individuals with increased risk of lung cancer. Lung cancer is the number one killer among cancers, with 160,000 deaths/year in the USA and 1.6 million/year worldwide. Early detection of lung cancer increases 5-year survival rate from 4% to 54%. Moreover, the...

A novel diagnostic test to identify individuals with increased risk of lung cancer.

Lung cancer is the number one killer among cancers, with 160,000 deaths/year in the USA and 1.6 million/year worldwide. Early detection of lung cancer increases 5-year survival rate from 4% to 54%. Moreover, the National Lung Cancer Trial (NLST) showed that early detection of lung cancer by low-dose CT reduces mortality by at least 20%. Despite recommendations for low-dose CT screening for heavy smokers fulfilling the NLST criteria, compliance is low. In addition, 80 million smokers and ex-smokers in the US who do not fulfil NLST risk criteria have no recommended solution.

The MyRepair test fulfils this unmet medical need by providing a quantitative prediction of lung cancer risk using a simple blood test. The test is based on a personalized measurement of the patient’s DNA repair capacity, a mechanism which is highly connected to the onset of cancer. Therefore, the MyRepair technology can potentially increase early detection of lung cancer and thus save lives.

 

Applications


A novel diagnostic test to identify individuals with increased risk of lung cancer


Advantages


·         Simplicity – MyRepair is based on a simple, cost-effective blood test.

·         Accessibility – Compared to low-dose CT which requires specific equipment, the MyRepair test can be easily integrated in general diagnostic labs and therefore may be more accessible to a larger portion of the population.

·         Additional applications – Since the test is based on measuring personalized DNA repair mechanism, it can be adopted in the future for the diagnosis of additional cancer types and DNA repair related diseases.


Technology's Essence


Based on the strong and well documented connection between impaired capacity for DNA repair and onset of cancer, the Livneh lab invented the MyRepair Test, a method for predicting lung cancer risk, based on measuring activity of 3 DNA repair enzymes.

Combining enzyme activities with experimental risk estimates generated MyRepair Score, which measures personalized DNA repair capacity of tested subjects.

An epidemiological/clinical study performed in Israel, further validated in an independent UK study, demonstrated that lung cancer patients have lower MyRepair Score than healthy people. In addition, subjects who test MyRepair-positive have an 85-fold higher risk to develop lung cancer compared to the general population.

Low MyRepair Score is a risk factor independent of smoking, and of comparable magnitude, indicating that it can be a prognostic tool for smokers, ex-smokers, and non-smokers.

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  • Prof. Zvi Livneh
1270
Monoclonal antibodies to IgE Description: Rat monoclonal anti-IgE antibodies that was generated by fusion of plasmacytoma (84.1C) or myeloma (EM953) cells with splenocytes of rat immunized with purified murine IgE mAb. The antibodies react with various IgE mAb of different specificities and not with...

Monoclonal antibodies to IgE

Description: Rat monoclonal anti-IgE antibodies that was generated by fusion of plasmacytoma (84.1C) or myeloma (EM953) cells with splenocytes of rat immunized with purified murine IgE mAb. The antibodies react with various IgE mAb of different specificities and not with immunoglobulins of other classes, and recognize an epitope on the murine Fc epsilon region.

Were shown to block IgE-Fc?R interactions and inhibit passive cutaneous anaphylaxis. 

Clone 84.1c recognizes a site on IgE, which is identical or very close to the Fc?R binding site. May be used for detection and manipulation of the IgE response in mice.

Reference:  Schwarzbaum S, Nissim A, Alkalay I, Ghozi MC, Schindler DG, Bergman Y, Eshhar Z. 1989. Mapping of murine IgE epitopes involved in IgE-Fc epsilon receptor interactions. Eur J Immunol 19(6):1015-23.

 

M182, M185, M186

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  • Prof. Zelig Eshhar
1655
Cellular senescence is a permanent cell cycle arrest induced by damage or stress applied on proliferating cells. In a cell autonomous manner, senescence is a potent barrier to tumorgenesis and contributes to the cytotoxicity of some anti-cancer drugs. However, with age senescence cells accumulate and...

Cellular senescence is a permanent cell cycle arrest induced by damage or stress applied on proliferating cells. In a cell autonomous manner, senescence is a potent barrier to tumorgenesis and contributes to the cytotoxicity of some anti-cancer drugs. However, with age senescence cells accumulate and promote a number of pathological conditions. Therefore the elimination of senescent cells is desired in order to prevent tumor- and inflammation- related pathologies and also to inhibit tissue ageing.
Today, our understanding of the mechanisms regulating the viability of senescent cells is limited. It has been suggested that senescent cells are resistant to apoptosis. Therefore, senescent cells elimination may be achieved by modifying the resistance to apoptosis of these cells.
Here the researches demonstrate the first feasible therapeutic approach that leads to eradication of senescent cells. Combination of direct induction of apoptosis in senescent cells with induction of cell death by pro-inflammatory repose induce by p21 knockdown will lead to reduction of viable senescent cells.

Applications


  • A therapeutic impact on inflammatory and fibrotic disease
  • Therapy for age-related disease such as type 2 diabetes, Alzheimer’s disease, Atherosclerosis, cataracts, Chronic obstructive pulmonary disease (COPD), and Osteoporosis

Advantages


  • Effective elimination of senescent cells- removal of senescent cells can prevent or delay tissue dysfunction and extend health span
  • Does not damage normal cells even at high concentrations

Technology's Essence


Researches demonstrated that the anti-apoptotic proteins Bcl-xL and Bcl-w level were elevated in senescence cells of both human and mouse origin. A subsequent study, in which Bcl-xL and Bcl-w were knocked down by siRNA, revealed that a combined knock down of Bcl-xL and Bcl-w had synergic effect, resulting in reduction of 50% in cell viability. Thus the increased level of anti-apoptotic proteins Bcl-xL and Bcl-w may account for the apoptotic resistance of senescent cells. p21 knockdown induced pro-inflammatory response and cell death in senescent cells.
Overall, the researchers show that combined inhibition of the anti-apoptotic proteins Bcl-xL and Bcl-w allows specific elimination of senescent cells and might be used to treat diseases where senescent cells are present. The researchers also found that the same effect might be achieved by reducing the expression of p21 in senescent cells. Integrating both approaches propose a more effective therapy.

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  • Prof. Valery Krizhanovsky

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