27 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
Gerber Doron
Cancer is the second leading cause of death globally. Matching proper treatment and dosage is crucial for a positive outcome. Any given drug may affect patients with similar tumors differently. Personalized medicine aims to address this issue. Unfortunately, most cancer samples cannot be expanded in culture, limiting conventional cell-based testing. Herein, presented is a microfluidic device that combines a drug microarray with cell microscopy. The device can perform 512 experiments to test chemosensitivity and resistance to a drug array. MCF7 and 293T cells are cultured inside the device and their chemosensitivity and resistance to docetaxel, applied at various concentrations, are determined. Cell mortality is determined as a function of drug concentration and exposure time. It is found that both cell types form cluster morphology within the device, not evident in conventional tissue culture under similar conditions. Cells inside the clusters are less sensitive to drugs than dispersed cells. These findings support a heterogenous response of cancer cells to drugs. Then demonstrated is the principle of drug microarrays by testing cell response to four different drugs at four different concentrations. This approach may enable the personalization of treatment to the particular tumor and patient and may eventually improve final patient outcome.
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.
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.
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)
Gerber Doron
We have a designed a new version of our cancer screening device. In this new version, we modified the device to work with a limited set panel of drugs (8-16). The idea is that we can take a panel of drugs the physician needs to choose from and test these drugs against cancer cells from a patient. We can then provide the physician with information on which drugs the patient's cancer cells are sensitive or resistant too. In turn the physician can now choose a more personalized therapy. The main difference from the former design is that it is not meant for hundreds of drug combinations and that it is designed with point of care diagnostics in mind.
Barda-saad Mira
The immune system employs intricate regulatory mechanisms to ensure that immune cells distinguish foreign invaders from healthy tissues via the ‘education’ process. Natural Killer (NK) cell education is of crucial interest due to its upcoming role in adaptive immunity. In individuals, 13%±6% of the NK cells do not express classical inhibitory receptors as killing inhibitory receptors (KIRs) superfamily and NKG2A. These dysfunctional cells, termed ‘anergic’ NK cells, have relatively lowered cytotoxic potential and reduced pro-inflammatory cytokine secretion. Most research has focused on the role of NK cell education, but the molecular framework underlying NK cell anergy or hypo-responsiveness phenotype remains unknown. Re-programming these cells and enhancing their functional role has great potential for cancer immunotherapy. Here we decipher the underlying molecular mechanism and identify key intrinsic regulators such as EGR2 and DGKα governing NK cell anergy. Together, reinforced by transcriptome analysis, we profile the anergic vs. responsive signature. Furthermore, we demonstrate that silencing these intrinsic regulators revokes NK functionality (cytotoxicity) , thus serving as markers for anergy or hypo-responsiveness and acting as a potential target to reverse dormancy. This newfound approach to “reprogram” them in situ via intrinsic regulators is of high clinical relevance for future NK anti-tumor immunotherapeutic approaches.
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.
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.
Garini Yuval
Analyzing stained tissue sections is of major importance for pathological diagnostics, and it forms a bottleneck in various clinical procedures, including cancer detection. Although there are now systems that can scan whole biopsies, they only measure color (RGB data) that provides limited information for reliable and accurate analysis. We invented a new modality for cancer analysis that is based on rapid spectral imaging measurement of whole biopsy, followed by adequate analysis. The spectral information at each pixel of the image is valuable and it allows to perform accurate analysis by using adequate algorithms. Using the system, we also identified the spectra of normal and cancerous cells from a lymph node sample of breast cancer biopsy. Using this information, we developed an algorithm that allows to identify cancer cells with high sensitivity and specificity. The method combines hardware for rapid scan of biopsies followed by specific way for detecting cancer from the measured spectral images.
Ilouz Ronit
The invention relates to a novel method and associated means for detecting and classifying prostate cancer based on an imbalance between the subunits of the enzyme Protein Kinase A (PKA) in MRI-targeted biopsy tissues. Based on experimental findings, we present an innovative biomarker system that enables precise distinction between benign tissue, low-grade (Grade Group 1), and high-grade (Grade Group 4 and above) lesions through spatial and quantitative measurement of the ratio between the regulatory subunit RIβ and the catalytic subunit PKA-C. The method is founded on the biochemical and spatial principle of structural integrity between PKA subunits. In healthy prostate tissue, RIβ and PKA-C co-localize along the basal cell layer, maintaining balanced holoenzyme architecture. In malignant lesions, however, RIβ is selectively lost while PKA-C becomes overexpressed and mislocalized within proliferating epithelial tumor cells. To quantify these differences, the invention comprises: Quantitative Immunofluorescence Imaging (IF) – enabling automated measurement of fluorescence intensity for each marker (RIβ, PKA-C, and basal cell markers) using a dedicated image analysis algorithm. Expression Ratio Analysis – computation of the quantitative RIβ:PKA-C ratio in defined regions of interest (ROIs) within each biopsy section, serving as a biological indicator of holoenzyme balance or imbalance. Biochemical Validation via Western Blot – confirming that the observed decrease in RIβ and increase in PKA-C are reflected at the total protein level in the same MRI-targeted biopsy samples. Future Development of Quantitative Thresholds and Decision Algorithms – the invention enables, in subsequent stages, the establishment of defined numerical thresholds for the RIβ:PKA-C ratio that may serve to automatically identify malignant or aggressive lesions and support diagnostic decision-making. By integrating spatial profiling with precise molecular quantification, the invention defines a unique biological signature that differentiates suspicious lesions from benign or indolent regions, independently of conventional histopathology. The invention further provides a basis for the development of a clinical diagnostic platform or laboratory kit designed to quantitatively assess PKA subunit imbalance in prostate biopsy specimens.
Knisbacher Binyamin
The invention presents methods for customizing chronic lymphocytic leukemia (CLL) treatment through the use of a detailed biomarker panel and specific agents, based on the patient's biomarker profile. This method aims to match patients with treatments likely to be effective, according to various markers from distinct categories (e.g., gene expression, protein expression, mutations, clinical features, disease subtypes), aiming to improve treatment precision and outcomes in CLL management. The approach suggests a shift towards personalized treatment, leveraging molecular characteristics to inform therapeutic choices in oncology. The results are, at least in part, based on dynamic BH3 profiling experiments, which were used in a comprehensive drug screen that tested 42 different FDA approved drugs on samples taken from dozens of CLL patients.
