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-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-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-003662 — Heterozygous mutations cause several genetic disorders. To correct the mutant allele, an HDR (homology directed repair) template is required since HDR initiation does not occur naturally. The IP, a new method to correct heterozygous mutations, does not require an HDR template. By using CRISPR and our specific gRNA design, we can singularly target the mutant allele to initiate HDR repair in heterozygous mutant genes. The IP has demonstrated efficacy in vitro having corrected several mutations, and it has the potential to correct any heterozygous mutation, including CD34+/ bone marrow related disorders and mutant VCP (valosin-containing protein) genes. In the latest stage of development, continued testing is the priority, and parties interested in gene-editing therapies stand to benefit from the IP’s progression.