37 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
Lellouche Jean-paul
"Effective Nanoscale Delivery System as an anti-Leishmania drug/technological platform for drug delivery"
Yadid Gal Moshe
We suggest for the first time a new treatment for withdrawal from drug addiction using a bacteria called Ruminococcus gnavus.
Cohen Cyrille
This is an optimized BCMA-specific chimeric antigen receptor for the treatment of multiple myeloma and other hematological diseases that we have developed.
Cohen Cyrille
TGFβ is a major immunoinhibitory factor present in the microenvironment of solid tumors. Different cancer types acquire the ability to overexpress TGFβ to escape immune response. Indeed, TGFβ dampens cytotoxic T cell activity, and its presence has been shown to correlate with tumor invasion and poor prognosis. Herein, we developed two approaches to target the effects of TGFβ and provide a functional advantage to genetically engineered T cells in the immunoinhibitory tumor milieu. We designed a TGFβRI-based co-stimulatory switch receptor (CSRI) that includes the TGFβ receptor I extracellular binding domain and a 4-1BB co-stimulatory signaling moiety. Additionally, we tested the function of a TGFβ-binding scFv trap produced by T cells. We demonstrated that both approaches endowed tumor-specific T cells with superior cytokine secretion, upregulation of activation markers, and reduced expression of inhibition markers upon co-culture with melanoma targets. Moreover, we noted that CSRI and the anti-TGFβ trap showed an improved anti-tumor function in vivo. Overall, we show that it is possible to target the TGFβ pathway to improve cellular immunotherapy.
Meital Gal Tanamy
Vaccines based on live attenuated viruses are the most effective strategy for controlling infections, since they elicit long-lasting natural and effective immune response, but entail challenges as safety and virulence. Hepatitis C Virus (HCV) is a major global health problem, causing liver diseases and liver cancer, with millions infected each year and hundreds of thousands of annual fatalities; but no vaccine is currently available for the virus. Here we present a novel computational approach for the accurate predication of virus attenuation. The approach is based on a rational design of weakened virus variants by insertion of high number of synonymous mutations to disrupt the viral RNA’s secondary structure and regulatory sequences important for the viral life cycle. By measuring RNA levels and virus spread in HCV infection model, we showed that these variants have lower viral fitness relative to the wild-type virus, with gradient of attenuation in concordance with the prediction model. Deep sequencing of replicating viruses demonstrated genomic stability of the attenuated variant. Differential expression analysis and evaluation of cancer-related phenotypes revealed that the variants have a lower pathogenic influence on the host cells, compared to the WT virus. These rationally designed variants may be further considered as a promising direction for a viable HCV vaccine. Importantly, the computational approach described here is based on the most fundamental viral regulatory motifs and therefore may be applied for almost all viruses as a new strategy for vaccine development.
Byk Gerardo
The nanohydrogels (NHGs)are new in away that they are biodegraded slowly after administration. The NHGs can be loaded with drugs such as amphoterycin B or voriconazole for treating fungal infections. The nanohydrogels are monodispersed particles of 100 to 400 nm that have the specialty to be both cross-linked and biodegradable tanks to special cross-linkers used fo their generation. The NHGs are loaded with drugs and display a slow release of the drug both in vitro and in cell assays. The drugs are delivered via intraperitoneal administration and protects the infected animals form lethal doses of fungi strains
Ayal Hendel
The invention is cellular based therapies for specifically targeting cells infected with viruses. In particular isolated T-cells and/or TCRs directed against various viruses, methods for their preparation and uses thereof for treating viral infections in subjects.
Onn Itay
We developed a peptide regulator that modulates the protein-protein interaction between Smc2 and Smc4 heads and blocks condensin activity. Condensin organizes interphase chromatin into mitotic chromosomes. This ensures the structural stability and segregation fidelity of chromosomes. Inhibiting condensin leads to a mitotic catastrophe and will affect cell proliferation. This property may be used to treat yeast infections and/or treat cancer directly or indirectly.
Ayal Hendel
The invention utilizes CRISPR-Cas9 editing and rAAV6 vectors for transgene delivery to correct the RAG1 and RAG2 coding exon. The novelty is in the construct we use for the correction which replaces the entire open reading from of the gene as oposed to standard practice which is to insert the transgene.
Piran Ron
The progressive loss of insulin-producing β-cells is central to the pathogenesis of all diabetes types, yet strategies for their regeneration remain limited. Here, we describe the successful implementation of a mathematical prediction we developed: inhibition of somatostatin (Sst) expression enabled robust, glucose-responsive β-cell regeneration and restored insulin independence in diabetic models. Genetic Sst knock out (SstKO) mice spontaneously recovered from chemically induced diabetes. We then rediscovered Cysteamine (Cys), an FDA-approved drug, as a pharmacological inhibitor of Sst production in mouse and human primary islets. Mechanistically, Sst suppression released a brake on intrinsic regenerative pathways within the islet. In diabetic wild-type mice, Cys reproduced the regenerative phenotype of SstKO animals. Importantly, in autoimmune-prone NOD mice, Cys treatment restored β-cell function and insulin independence. Together, these findings identify Sst inhibition as both a regenerative and therapeutic axis for β-cell regeneration, and nominate Cys as a safe, clinically translatable candidate for diabetes therapy
Cohen Cyrille
In this project, we have developed novel chimeric receptors by fusing the extracellular domain of the murine 14G2a antibody with various signaling domains and expressing them in primary human T-cells. Through our work, we identified several mutants exhibiting enhanced biological activity against breast cancer, neuroblastoma, melanoma, and other cancer types. Additionally, we demonstrated that these receptors can upregulate the activation marker 41BB. Overall, we propose that the engineering of T-cells with improved anti-GD2 chimeric receptors holds significant implications for enhancing T cell-based immunotherapy. These mutants also serve as a potential foundation for the development of antibodies or bispecific T-cell engagers (BiTEs)
Piran Ron
Latent autoimmune diabetes in adults (LADA) is a relatively new defined diabetes type. It has a strong autoimmune component, making it similar to type I diabetes (T1D), while its onset is at a later age (30’s or older), making it similar to type II diabetes (T2D). It is still unclear how prevalent LADA is in the general population, as most LADA patients are erroneously diagnosed with T2D receiving imprecise treatment. It is estimated that most lean T2D patients are LADA patients. Therefore, it is estimated that the percentage of LADA patients out of the T2D patients is 10%. Considering that T2D is 90% of all diabetic patients and that T1D is about 8%, making LADA more abundant than T1D (10*90/100=9% of total diabetic patients). All diabetes types eventually end in pancreatic β-cell loss and thus results in the loss of insulin secretion, which causes overproduction and a decreased cellular uptake of glucose. Therefore, developing novel strategies aiming to protect, regenerate, and restore β-cells would represent a promising therapeutic alternative for all patients with diabetes. Researches have identified several drugs which possibly stimulate β-cell proliferation and enhance their function. Among these are γ-Aminobutyric acid (GABA), dipeptidyl peptidase IV inhibitors (DPP-4i) such as Sitagliptin (SIT), or proton pump inhibitors (PPI) like Omeprazole (OMP). We found that the combined treatment (CT) administration demonstrated a significant improvement in diabetic symptoms compared to untreated mice and mice that received GABA, GABA+SIT, GABA+OMP, or SIT+OMP. Moreover, ~30% of the mice that were given CT were COMPLETELY CURED of diabetes and showed normoglycemia for 7 weeks after the last drug administration, an unprecedented achievement for this irreversible disease. We have clear indications that similar success rates also recapitulate in human LADA patients. The challenge was to differentiate the 30% cured from CT unresponsive mice. Thus, we repeated the CT experiment, this time taking blood samples from all mice after diabetes onset but before starting treatment. After the experiment, we returned to the blood samples and arranged them according to the cured/unresponsive. We identified circulating RNA markers that predict 100% response to CT, enabling the successful identification of candidates for CT.
