38 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
Levanon Erez
Recent findings suggest that ICIs fail to invoke an immune response when the tumors lack potent immunogenic peptides called “neoantigens”. The majority of mutations in cancer result in only slightly modified peptides that are unlikely to serve as neoantigens and trigger an immune response – despite checkpoint inhibitor treatment. To overcome this limitation, we developed a computational framework that aids the design of synthetic polymers, called antisense oligonucleotides (ASOs), that manipulate the splicing process in tumor cells to offset protein synthesis machinery and force production of entirely new peptides. Smart, computationally driven, choices of potential targets, will result in highly immunogenic peptides. We expect the combination of our technology with current checkpoint inhibitors, to offer a new and effective strategy in cancer therapy.
Cohen Cyrille
In this invention, we have identified a gene involved in amino acid metabolism that when over-expressed in primary human lymphocytes, enhances T-cell function
Ayal Hendel
Tumor-Infiltrating Lymphocyte (TIL) therapy has emerged as an effective personalized treatment for advanced melanoma. However, several obstacles hinder its optimal implementation in clinical practice. The advent of CRISPR gene editing presents a promising avenue for enhancing TIL therapy by improving the ability of lymphocytes to target tumors more effectively. By making precise modifications to immune cells, it is possible to boost significantly their efficacy in combating cancer. Specifically, the simultaneous targeting of CBL-B and CBL immune checkpoints in CRISPR-modified TILs has demonstrated increased production of cytotoxic molecules and cytokines, thereby enhancing their capability to eradicate cancer cells directly. This innovative approach has the potential to lead to improved clinical outcomes for a broader range of patients with melanoma.
Cohen Cyrille
In this invention, we have identified several genes that are part of the glucose metabolism that when expressed in primary human lymphocytes, enhance T-cell function
Cohen Haim
This invention relates to a method for diagnosing Covid-19 virus in biological samples. Specifically, this invention relates to a method for detecting SARS-CoV2 viral RNA using a fluorescently labeled complementary DNA probe according to a phenomenon known as Microscale Thermophoresis (MST). MST is a physical phenomenon where biomolecules migrate differently along a temperature gradient according to properties such as size, hydration shell and charge. These different migration patterns resulting in a separation along the gradient which can be quantified for scientific studies. Since binding events are predicted to affect thermophoretic migration, MST is used to detect biological interactions such as protein-protein and protein-ligand interactions with high accuracy and low sample consumption. In a typical MST measurement an infra-red laser (I.R) is used to create the temperature gradient for a limited time and one of the binding partners is fluorescently labeled and being monitored during the total time of the experiment. The ratio between the florescence signal before and during the temperature gradient is calculated and represents the thermophoretic migration. The present invention is directed to utilize this phenomenon, prior MST measurement RNA is extracted from a biological sample using guanidinium thiocyanate phenol-chloroform extraction technique. Then, under strict conditions to ensure maximum specificity it is allowed to hybridize with a fluorescently labeled SARS-CoV2 DNA probe. If the viral RNA is present in the sample, a RNA:DNA hybrid is formed and the difference between the thermophoretic migration of a free probe and the hybrid is measured using an MST instrument. For more details and proof of concept’ please see figure 1-4. The method of this invention allows a detection time of 3 seconds for 1 sample, meaning a theoretical capacity up to 58,000 samples per day for 1 MST instrument (depends on the model in used). The invention is also further applicable for the diagnosis of other viruses and bacteria.
Sol Efroni
The invention is a computational framework that predicts a subject's biological age and immunological state directly from the sequence composition of their T-cell receptor (TCR) β-chain repertoire. It combines two complementary feature representations - age-associated clonotype abundances and CDR3 amino-acid 3-mer frequencies - which are processed through an ensemble of gradient-boosted trees for feature selection and a deep multi-layer perceptron (MLP) neural network for regression. A novel signed-Wasserstein distance scoring method identifies individual TCR clonotypes statistically biased toward younger or older donors, creating an interpretable molecular 'aging vocabulary' that feeds the predictive model. The system achieves robust cross-cohort age prediction (MAE ≈ 6–7.5 years, R² ≈ 0.67–0.78) and reveals a reproducible ~1.5-year sex-related immunological offset, with the capacity to reconstruct a subject's history of viral exposures from the TCR repertoire alone.
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.
Gerber Doron
We have invented a microfluidic mechanism that allows us to take any ELISA/antibody based detection assay and improve its sensitivity 2-3 orders of magnitude. This means that we can work with very small samples or discover for example blood markers that are very scarce.
Shamay Meir
Distal cis-regulatory elements, such as enhancers and silencers, dictate tissue-specific complex transcriptional repertoire in an orientation- and position-independent manner. Herpesviruses show programmed latent and lytic gene expression based on the infected tissue and physiological cell state. In a recent study we systematically identified the enhancers within the Kaposi’s Sarcoma-associated Herpesvirus (KSHV) genome. Here, we present ENHAvir, an NLM-based tool that can successfully predict the enhancers in a viral genome. We used the DeBERTa v3 language model56 in our framework. DeBERTa v3 is an encoder-style language model, making it a suitable candidate for extracting representations that could be used for new tasks. ENHAvir successfully identified known and novel enhancer elements in the herpesviruses, namely, EBV, HSV1, HSV2, VZV, HCMV, HHV-6, HSV-7, and MHV68. ENHAvir learned the minute patterns of previously published KSHV enhancers and their adjacent sequences responsible for enhancer looping. The activity of the predicted enhancers was validated by cloning the ENHAvir predicted sequences on the EBV genome downstream to the luciferase gene in a reporter plasmid with a weak promoter and performing dual-luciferase reporter assays in EBV-infected and uninfected cell lines. Interestingly, ENHAvir also precisely identified enhancers with the human genome, and examples for Fos, Jun, DPPA3, and Myc genes are presented. The ability of ENHAvir to predict both viral and cellular enhancers, provides an additional layer to the complex gene regulation via viral enhancers but also points out the evolutionary conservation of enhancer micro-signatures between a virus and its host.
Cohen Cyrille
We have developed an improved T-cell receptor targeting the NYESO1 antigen to generate a T-cell based therapy for cancer.
Cohen Yigal
We discovered a new gene in basil Pb2 which controls resistance against downy mildew.
Meital Gal Tanamy
Hepatitis C virus (HCV) is a major public health concern, with about 60 million people infected worldwide, who are at risk for developing life-threatening liver disease. No vaccine is available, and immunity against the virus is not well understood. HCV usually causes chronic infections. However, 20-40% of infected individuals experience spontaneous recovery, suggested to be mediated by HCV-specific immunity. Therefore, comparing immune responses between spontaneous clearer (SC) and chronically infected (CI) individuals may identify mechanisms governing successful viral clearance and lead to designing effective vaccines. It is now widely accepted that broad neutralizing antibodies that cross neutralize heterogeneous viral isolates play a key role in HCV clearance. However, since most of the HCV-neutralizing antibodies developed and characterized to date were isolated from CIs, the nature and epitope specificities of nAbs in SC HCV infections are not well understood. We recently revealed novel distinct epitopes that are associated with infection clearance. To identify the linear immunodominant epitopes associated with viral clearance, we employed an unbiased approach. We screened a phage-display library presenting random peptides to detect binders to antibodies in serum samples from SC and CI HCV infections. This methodology enabled us to capture a comprehensive view of the various immunodominant epitopes in each patient group and compare between them. We identified three SC-unique epitopes that were synthetically synthesized as peptides and validated that these are immunodominant neutralization epitopes specifically in SCs. Importantly, we showed that these epitopes may be efficiently represented by linear peptides, an important observation considering that most of the HCV neutralization epitopes are conformational. by in vivo experiments were we immunized mice with these peptides, we validated their ability to elicit an anti-HCV antibody-mediated immune response. Importantly, we showed that SC-unique epitopes induced a broader and stronger neutralization response compared to other known epitopes. The mixed-peptides sera exhibited the highest neutralization capacity across almost all HCV genotypes. Therefore, this rational design of anti-HCV peptide vaccine induces a broad and efficient antibody immune response.
