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-003676 — The IP introduces a novel methodology aimed at tackling autosomal dominant genetic disorders. By harnessing the power of CRISPR technology and guided RNA (gRNA) design, this IP offers a targeted approach to address mutant alleles while preserving the expression of healthy alleles. It can precisely target mutant alleles associated with autosomal dominant disorders, paving the way for potential therapeutic interventions. Unlike conventional approaches, this methodology leverages specific gRNA design, incorporating mutated sequences adjacent to the protospacer adjacent motif (PAM) sequence. This allows for the selective targeting of mutant alleles and minimizes off-target effects and preserving the expression of healthy alleles. At its current stage, proof-of-concept experiments have demonstrated the efficacy of gRNAs targeting mutant alleles associated with specific disorders. Future development efforts will focus on expanding the scope of application to other autosomal dominant genetic disorders and refining the methodology for clinical translation. Its tailored approach to gRNA design offers enhanced precision and specificity, reducing the risk of unintended genetic modifications. The IP has broad utility and commercial potential; the versatility of CRISPR technology allows for its potential application in a wide range of autosomal dominant disorders beyond the initial target.

TS-003675 — The IP is pioneering chimeric antigen receptor (CAR) technology to target Nucleolin (NCL) expressing T cells, and it has the ability to pinpoint NCL, an untapped antigen in cancer immunotherapy, for CAR-T cell targeting. By crafting CARs designed to target NCL and expressing them on T cells’ surface, this technology showcases promising anti-tumor activity against a spectrum of cancer types. At its current conceptual stage, proof-of-concept experiments have demonstrated successful targeting of breast cancers. Further endeavors are planned to validate the efficacy and specificity of CAR-T cells against numerous other cancers through meticulous in vitro and in vivo assays. Its innovative approach in targeting NCL broadens the horizons of cancer treatment, potentially diversifying the therapeutic options available to patients. The adaptable nature of CAR-T cells enables the targeting of various cancers, including breast, lung, brain cancer, myeloid, and lymphoid leukemia, among others.

TS-003674 — The IP focuses on the development of chimeric antigen receptor (CAR) targeting Nucleolin (NCL) expressing natural killer (NK) cells, offering a novel approach to cancer treatment. It has the ability to target NCL, a novel antigen in cancer immunotherapy that has not been previously utilized as a target for CAR-NK cells. By designing CARs targeting NCL and expressing them on the surface of NK cells, this technology demonstrates promising antitumor activity against various cancer types. The stage of development for this IP is currently conceptual, with proof-of-concept experiments demonstrating successful targeting of breast cancers. Further work is planned to verify the efficacy and specificity of CAR-NK cells against multiple other cancers through in vitro and in vivo assays. Its novelty in targeting NCL opens up new possibilities for cancer treatment, potentially expanding the repertoire of available therapies for patients. Additionally, the versatility of CAR-NK cells allows for targeting a wide range of cancers, including breast, lung, brain cancer, myeloid, and lymphoid leukemia, among others.

TS-003673 — The IP focuses on pairing oncolytic viruses with engineered adoptive cell therapies, such as CAR-T and CAR-NK cells, to enhance their anti-tumor capabilities within challenging tumor microenvironments. The significance of this IP lies in its ability to address several key challenges in cancer immunotherapy. By engineering the oncolytic virus to express T cell activating cytokines and modifying T or NK cells to interrupt inhibitory pathways while inserting genes regulated by virus-expressed factors, this approach aims to improve the safety and efficacy of engineered cell therapies. Additionally, the use of SynNotch technology for regulated gene expression is a novel strategy for enhancing therapeutic specificity and activity. The stage of development for this IP is currently at the conceptual and prototype phase, with further work planned for validation and refinement. The IP offers compelling advantages over existing methods. Its safety, specificity, and activity (coupled with the ability to regulate cell function using oncolytic viruses) appeal to biotechnology and pharmaceutical companies seeking innovative cancer therapies. The potential applications of this technology extend beyond CAR expression, paving the way for future developments in targeted cancer immunotherapy and gene regulation.

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-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.