TS-003705 — This IP solution aims to enhance the efficacy of Natural Killer (NK) cell therapy in cancer immunotherapy. By targeting the ADAM17 gene using CRISPR technology, it intends to maintain the expression of CD16 on NK cells, crucial for antibody-directed cell cytotoxicity (ADCC) against tumor cells. Cryopreserved ADAM17 knockout (KO) NK cells demonstrated significantly higher CD16 expression post-thaw, leading to enhanced ADCC against cancer cell lines when combined with antibodies. This advancement addresses a critical issue in cancer immunotherapy and ensures sustained antitumor activity of NK cells even after cryopreservation. It holds potential applications in various off-the-shelf adaptive NK cell products, catering to a wide range of cancer types and patient needs. Companies in cellular immunotherapy may find this IP valuable for developing next-generation NK cell therapies with improved efficacy and versatility. With further development and testing planned—including evaluation in in vivo models and expansion using different cytokines—the IP presents a promising avenue for advancing cancer treatment strategies.

TS-003693 — CD34+ Bone Marrow Stem Cells for the Treatment of Chronic Granulomatous Disease (CGD) Chronic Granulomatous Disease (CGD) is a genetic disorder characterized by defective immune cells unable to produce Reactive Oxygen Species (ROS); this compromises someone’s ability to fight infections. Current treatments, such as antimicrobial prophylaxis, only partially address the condition. This IP proposes a novel approach utilizing CRISPR/AAV technology to genetically edit autologous CD34+ bone marrow stem cells ex-vivo, aiming to restore the normal function of immune cells and improve clinical outcomes for CGD patients. The technology involves off-the-shelf CRISPR guide RNAs (gRNAs) targeting mutated genes in CGD, along with adeno-associated virus (AAV) vectors delivering healthy copies of these genes. This technology offers a promising solution to the limitations of existing CGD treatments by addressing the root cause of the disease at the genetic level. By genetically editing autologous CD34+ stem cells ex-vivo, the technology seeks to produce functional immune cells capable of effectively combating infections in CGD patients. This approach has the potential to significantly improve the quality of life and life expectancy of CGD patients, offering a new avenue for personalized medicine in the treatment of genetic disorders. Compared to conventional treatments (e.g., antimicrobial prophylaxis) this gene therapy approach offers the advantage of directly addressing the underlying genetic defect in CGD. By utilizing CRISPR/AAV technology, the off-the-shelf materials provided can efficiently target and replace mutated genes in CD34+ stem cells, potentially resulting in a higher percentage of ROS production and improved immune function. Further development of this technology involves generating corrected CD34+ stem cells targeting the CYBB, CYBA, NCF1, and NCF2 genes associated with CGD mutations. These corrected cells will be tested in preclinical models to assess their antimicrobial activity and therapeutic efficacy. Ongoing research will focus on optimizing the gene editing process and expanding the application of the technology to other genetic disorders beyond CGD. Pharmaceutical companies specializing in gene therapy, immunology, and rare diseases are likely to be interested in licensing this technology for further development and commercialization.

TS-003689 — This IP exhibits a significant advancement in cancer immunotherapy. It encompasses a novel scFv designed to specifically target CD33, a surface antigen commonly expressed in hematologic cancers such as leukemia, myeloma, and lymphoma. This scFv serves as a fundamental component in various therapeutic modalities, such as chimeric antigen receptor (CAR) T-cell and natural killer (NK) cell therapies. Hematologic cancers pose significant challenges in treatment and often require targeted therapeutic approaches. The scFv targeting CD33 offers a promising solution by enabling the development of highly specific immunotherapies. CAR-T cells and CAR-NK cells engineered with this scFv can selectively recognize and eliminate CD33-expressing cancer cells while sparing healthy tissues, thus potentially improving treatment efficacy and minimizing adverse effects associated with traditional therapies. The IP’s innovative design features an alternative linker and an unexpected reverse orientation of the variable heavy (VH) and variable light (VL) chains, potentially conferring advantages in terms of binding affinity and epitope recognition. This enhances the specificity and effectiveness of CD33-targeted therapies, offering improved treatment outcomes for patients. The applications of the scFv targeting CD33 are extensive and includes both immediate and future uses. In the short term, it can be incorporated into CAR-T cell and CAR-NK cell therapies for the treatment of CD33-positive hematologic cancers. Additionally, the scFv may find utility in the development of other CD33-targeted therapies—including bispecific antibodies and antibody-drug conjugates—expanding its therapeutic potential across a broader range of malignancies. Biopharmaceutical companies involved in cancer immunotherapy may express interest in licensing this innovative technology. Further development of the scFv targeting CD33 involves in vivo assays to evaluate its efficacy against human hematologic cancer xenografts in animal models. Ongoing research efforts will focus on optimizing the scFv sequence and engineering CAR-T and CAR-NK cells expressing this scFv for preclinical and clinical studies. These endeavors aim to establish proof of concept and advance the technology towards eventual clinical translation.

TS-003681 — The IP revolves around the development of CD70 knockout natural killer (NK) cells and their integration with CD70 chimeric antigen receptor (CAR) technology to overcome fratricide—a phenomenon where CAR-expressing NK cells attack each other. This method employs gene editing techniques like CRISPR and AAV to target the CD70 gene and integrate CAR constructs into the CD70 locus of NK cells. The IP aims to enhance the effectiveness of CAR-NK cell therapy, particularly in the context of CD70-positive tumors. By eliminating CD70 expression in NK cells and simultaneously integrating CAR constructs into the CD70 locus, it mitigates fratricide, thereby enhancing the survival and functionality of engineered NK cells in the tumor microenvironment. Unlike existing methods, which may suffer from fratricide when CAR-NK cells target antigens present on their own surface, the IP offers a unique solution by leveraging the CD70 gene as an integration site for CARs. This strategy not only overcomes fratricide but also enhances the specificity and potency of CAR-NK cells, potentially leading to improved therapeutic outcomes. The IP holds promise for various cancer types, including glioblastoma, T cell lymphomas, and B cell malignancies, where CD70 expression is prevalent. Additionally, the modular nature of CAR-NK cells allows for customization to target different antigens, broadening its application across diverse malignancies. The market for personalized cancer treatments continues to grow, making this technology highly attractive for commercialization. The IP has demonstrated successful generation and functionality of CD70 knockout/CD70 CAR-NK cells, progressing from conceptualization to proof of concept. Further development involves characterization and optimization of these engineered NK cells for clinical translation.

TS-003672 — The IP introduces a significant advancement in cancer immunotherapy by enhancing the efficacy of natural killer (NK) cells in targeting tumors within challenging microenvironments characterized by xenobiotic exposure and hypoxia. This approach involves genetically modifying NK cells to disrupt the aryl hydrocarbon receptor nuclear translocator (ARNT) protein using the Cas9/RNP method. By doing so, it aims to counteract the inhibitory effects of the AhR and HIF1α signaling pathways, thereby augmenting the anti-tumor capabilities of NK cells. The IP holds substantial benefits for cancer treatment. By equipping NK cells with improved resilience against environmental stressors, it offers the potential for more effective and targeted therapeutic interventions, particularly in cases where conventional treatments may prove inadequate. Additionally, the ability to modulate NK cell functionality provides a personalized approach that leverages the innate anti-tumor properties of these cells. There are opportunities for biotechnology and pharmaceutical companies specializing in cancer therapeutics to benefit from the IP, which is currently at the proof of principle stage. The scalability and adaptability of this IP extend its market potential beyond cancer therapy to encompass a broader range of immunological and pathological conditions.

TS-003671 — This is a new approach in genetic engineering focused on overcoming acute Graft versus Host Disease (aGVHD) in gene-modified immune effector cells. By using micro RNA155 (miR155) as the integration site for CAR-T cells, this technology aims to enhance the functionality and specificity of immune cells. It involves the integration of DNA encoding CARs into the miR155 gene locus using Cas9/RNP+AAV, resulting in simultaneous gene knockout and CAR knock-in with high efficiency. This universal construct, facilitating the insertion of any transgene into human primary T cells, is a breakthrough in cell therapy. The IP has potential applications in various blood cancers, offering dual specificity and enhanced function of CAR-T cells. The development team plans to further characterize the functionality of MIR155 KO-CD33CAR-T cells through in vitro and in vivo studies.

TS-003670 — The IP is an innovative approach in cellular therapy safety assurance. It addresses concerns regarding residual feeder cells in therapeutic immune cell products, which may pose risks such as unregulated immune activation and proliferation. Leveraging the unique attributes of the K562 cell line, commonly used as a base for feeder cells, the assay utilizes quantitative PCR (qPCR) targeting specific markers like BCR-ABL or transgenes for sensitive and rapid detection of residual feeder cell contamination. This method offers higher sensitivity and faster results compared to existing assays and leverages clinically-validated qPCR techniques for enhanced safety screening. Development has reached the proof of principle/prototype stage and is poised to address critical safety concerns in cellular therapy manufacturing. The assay’s potential applications span across the cellular therapy landscape.

TS-003668 — This IP centers on a natural killer (NK) cell function, specifically the identification of interleukin 1 receptor antagonist (IL-1ra) as a potential biomarker. The research highlights the secretion ability of IL-1ra in response to NK cell stimulation by phytohemaglutinin, indicating optimal NK cell function. It offers significant advantages over existing methods, providing a quick, simple, and inexpensive assay to select potentially optimally functional NK cells for cancer therapy augmentation. The stage of development is conceptual and proof of principle with further work planned to characterize IL-1ra secreting donors and explore associated mechanisms. Notably, this finding has not been reported elsewhere, positioning it as a potential replacement for complex cytotoxicity assays in assessing NK cell function. Commercial applications include selecting allogeneic hematopoietic stem cell donors and off-the-shelf cellular therapy for cancer patients.

TS-003667 — This is a new method for genome editing gamma delta T cells to generate off-the-shelf gamma delta CAR-T cells for cancer immunotherapies. The approach utilizes Cas9/RNP and AAV to achieve highly efficient gene knockout and site-directed gene and CAR insertion in gamma delta T cells. The process involves the use of mb-IL21 expressing feeder cells for the expansion of gene-edited cells. This is a significant advancement in the field, with potential applications in cancer immunotherapy, and further development aims to validate the antitumor activity of these cells in vitro and in vivo.

TS-002302 — Acute myeloid leukemia (AML) causes myeloid cells to interfere with the production of healthy white blood cells, red blood cells and platelets; patients will experience fatigue, easy bruising, infections, etc. Due to expansion ex vivo with IL-15, AML patients and donors’ natural killer (NK) cells have an increase in glycogen synthase kinase 3 beta (GSK3β) from the loss of cytotoxicity and defective metabolism. Researchers at Nationwide Children’s Hospital targeted GSK3β in NK cells to promote antitumor activity by expanding NK cells with feeder cells expressing membrane-bound IL-21 without altering the GSK3β levels. They deleted GSK3β using the cas9/RNP and expanding paired-donor knock out and wild-type NK cells. When assessing transcriptional and functional alterations induced by the loss of GSK3β, GSK3β-KO cells demonstrated changes in gene expressions that suggested possible metabolic reprogramming and exhibited 150% higher spare respiratory capacity, a marker for metabolic fitness. By using mbIL21 expansion in the expansion of NK cells and GSK3β in these cells, the upregulation of GSK and drug inhibitors is prevented.