27 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
Yissachar Nissan
The invention relates to the identification and use of a unique gut microbes configuration that inhibits tumor growth and enhances the efficacy of immune checkpoint inhibitors (ICIs) in metastatic melanoma patients. By utilizing specific gut bacterial strains with immunomodulatory properties - it is possible to predict clinical response prior to immunotherapy, enhance anti-tumor immune responses, overcome treatment resistance, and improve therapeutic outcomes in patients with resistant cancers. Specifically, the invention focuses on a defined consortium of bacterial strains identified through a series of experiments conducted in our laboratory (by analyzing intestinal responses to patients microbiota samples using our unique gut organ culture system). This microbial mix includes Barnesiella intestinihominis, Ruminococcus callidus, Ruminiclostridium siraeum, and additional strains predicted to induce pro-inflammatory immune responses that potentiate enhanced anti-tumor immunity. The invention further comprises a novel experimental pipeline for identifying beneficial gut bacterial strains from among the thousands found in patient microbiome samples, aimed at boosting immune system activity and improving the success of anti-cancer treatments.
Cohen Cyrille
We have developed an improved T-cell receptor targeting the NYESO1 antigen to generate a T-cell based therapy for cancer.
Gil Hava
The invention consists of (i) discovery that tumor metastasis of breast and other forms of cancer can be prevented by inhibiting the interaction between cortactin and the non-receptor tyrosine kinase Pyk2, (ii) a 19-mer peptide derived from the Pyk2 sequence is an inhibitor of this interaction, (iii) administration of this peptide significantly reduces metastasis in malignant cell-lines and in immune-competent mice, and (iv) additional peptides with improved inhibition profiles were derived in a structure-based approach.
Cohen Cyrille
In this project we have generated novel targeting chimeric receptors based on the extra cellular domain of two members of the SIGLEC family: SIGLEC7 and SIGLEC9. These targeting moieties were fused to different signalling domains and expressed in primary human T-cells. We identified for each SIGLEC receptor the optimal molecules and went on and performed multiple functional assays. We observed enhanced cytokines secretion and recognition of multiple tumors (ovarian cancer, cervical cancer, lung cancer) mediated by SIGLEC chimeras. We also demonstrate that these receptors can upregulate the activation marker 41BB as well as display significant anti-tumor cytotoxicity, upon co-culture with tumor cells. Overall, we propose that engineering T-cells with a SIGLEC-based chimeric receptors bears important implications for the improvement of T cell-based immunotherapy.
Cohen Cyrille
The invention involves the computational design and development of novel constant regions for human T-cell receptors (TCRs), termed "Structurally Enhanced TCR" (SET). By introducing a set of strategic mutations into the TCR constant domains, the SET design improves receptor stability, enhances surface expression, increases functional avidity, and ensures preferential pairing of the α and β chains, minimizing mispairing with endogenous TCRs. This innovation offers a universal platform to optimize T-cell therapies for cancer and infectious diseases without requiring additional gene editing.
Barda-Saad Mira
The focus of this patent application is the development of a novel therapeutic approach for controlling and improving NK cell killing of cancer cells or viruses in vivo by suppressing the key negative regulators of NK cell cytotoxicity. Natural-killer (NK) cells represent a powerful weapon of immune defense against viral infections and tumor growth, via cytotoxicity of target cells. Specifically, NK cells are particularly efficient in removing metastatic cells and tumor grafts. We recently revealed that NK cell response is inhibited by two main mechanisms: (1) dephosphorylation of signaling molecule by the protein tyrosine phosphatase SHP-1, and (2) ubiquitylation mediated degradation of signaling molecule by the E3 ubiquitin ligases c-Cbl and Cbl-b. These molecular events block NK cell activation; however, their suppression increases NK cell cytotoxicity of cancer cells. NK cell-based immunotherapies represent a promising strategy to combat cancer, yet, no clinical trial has demonstrated a significant benefit in malignancies. Our novel approach for improving NK cell killing of cancer cells is composed of an in vivo NK-targeted drug-delivery system that strike the molecular mechanisms that inhibits NK cell activation, i.e. SHP-1 and the Cbls, using specific siRNA. To specifically target the NK cells, the siRNA will be coupled to nanoparticles coated with specific antibodies to NK cells.
Cohen Haim
To explore the role of protein post-translational modifications on lifespan and healthspan , we developed the PHARAOH computational tool based on the 100-fold differences in longevity within the mammalian class. Analyzing acetylome/phosphorylome and proteome data across 107 mammalian species identified 482 and 695 significant longevity-associated acetylated lysine residues in mice and humans, respectively. In addition, we have recognized 2115 longevity associated p phosphorylations. In regards to acetylations, these sites include acetylated lysines in short-lived mammals that were replaced by permanent acetylation or deacetylation mimickers, glutamine or arginine, respectively, in long-lived mammals. Conversely, glutamine or arginine residues in short-lived mammals were replaced by reversibly acetylated lysine in long-lived mammals. For phosphorylations, site these sites include phosphorylated Serine (S), Tyrosine (Y) and threonine (T) or their replacement to aspartic acid (D) or glutamic acid (E)or Alanine (A) and Y to phenylalanine (Y to F). Pathway analyses of the acetylation sites highlighted the involvement of mitochondrial translation, cell cycle, fatty acid oxidation, transsulfuration, DNA repair and others in longevity. A validation assay showed that substitution of lysine 386 with arginine in mouse cystathionine beta synthase, to attain the human sequence, increased the pro-longevity activity of this enzyme. Likewise, replacing the human ubiquitin-specific peptidase 10 acetylated lysine 714 with arginine as in short-lived mammals, reduced its anti-neoplastic function. These findings provide a computational tool for identifying modifications that control longer healthy life and potential interventions to extend human healthspan.
Popovtzer Rachala
We have recently developed a new imaging technology, which is similar to FDG-PET, yet is cancer specific, and provides the ability to distinguish between cancer and metabolically active inflammatory processes. This novel technology utilizes glucose-functionalized gold nanoparticles (GF-GNP) as metabolically-targeted CT contrast agents. It sensitively discriminates between tumors and inflammation due to the unique biodistribution and pharmacokinetic profile of nanoparticles, and due to dissimilarities in angiogenesis occurring under the different pathologic conditions. Unfortunately, gold nanoparticles are far from being used in clinical trials due to the high risk of accumulation and long-term toxicity. For this reason, an advanced nanocarrier for immediate clinical use must be developed. In the present project, we propose to develop nanocarriers which will be composed of FDA-approved, biodegradable polymeric materials, coated with glucose. By modifying the surface of these nanocarrie
Moran Dvela Levitt
TMED proteins are implicated as oncogenic proteins in brain tumors and a variety types of additional tumors. We found that inhibition and downregulation of members of the TMED family, pharmacologically through treatment with the preclinical drug BRD4780, or genetically through siRNA or KO exert anti-tumor effect. This includes decrease in growth, migration and aggressiveness and targeting of cancer stem cell self-renewal. Additionally, TMED targeting increases treatment sensitivity to chemotherapy in different types of brain tumors including glioblastoma or pediatric brain tumors such as Diffuse Intrinsic Pontine Glioma (DIPG).
Popovtzer Rachala
The next generation FDG-PET, based on radioactive
Efroni Sol
גילוי מוקדם של סרטן בעזרת כימות רפרטואר תאי טי
Fixler Dror
Light-tissue interaction is common in clinical treatments and medical researches, therefore the investigation of light path in irradiated tissue is of high importance. The innovation of this application rises from the combination of two different research areas: theoretical models of light path in irradiated tissues (Diffusion Reflection- DR) and the optical properties of gold nanoparticles. These theoretical models, which were developed about twenty years ago, suggested different reflection profiles for different tissue structures. Still, a diagnostic tool for cancer detection, based on these theoretical models, was still not developed. The use of gold nanoparticles as absorption contrast agents introduces the DR measurements of tumors as a highly sensitive, simple method for cancer detection purposes
