TS-003707 — This IP enhances anti-tumor immune responses using a chimeric herpes simplex virus (HSV) expressing human interleukin 21 (hIL21). The virus, designated as C021, is engineered to express hIL21, which is inserted into the ICP34.5 locus under the control of a potent MND promoter. Unlike previous generation oHSV, the transcripts produced by C021 are actively translated into cytokines within the tumor environment, leading to higher levels of cytokine production. Preliminary studies in immune-competent mouse tumor models have demonstrated that the expression of IL21 by C021 enhances immune-mediated anti-tumor activity. It increases Natural Killer (NK) and T cell activity in both flank and orthotopic brain tumor models. Additionally, C021 augments the interferon-gamma (IFN-γ) response of NK and CAR-NK cells, with ongoing studies anticipated to show similar effects on CAR-T cells. This versatility positions C021 as a standalone therapeutic or as a complementary treatment alongside adoptive cellular or engineered cellular therapies. The advantages of C021 over existing methods include improved immune activity and anti-tumor efficacy, making it a promising candidate for cancer therapy. Its potential applications extend to CAR therapy markets and beyond, given its compatibility with various engineered cytotoxic therapies.

TS-003700 — This IP revolves around utilizing oncolytic viruses (OVs) to enhance adoptive cellular therapy (ACT) for combating various cancers. Specifically, the innovation focuses on employing oncolytic herpes simplex viruses (oHSV) to selectively target cancer cells, triggering a chemokine and inflammatory response, thereby attracting immune cells to the infected site and bolstering their activity against the tumor. By precisely timing the oHSV infection and engineering the virus to express elevated levels of specific cytokines, notably interleukin-21 (IL-21), the effectiveness of cellular therapies, such as CAR-T and CAR-NK, in targeting cancer cells is significantly improved. This IP holds promise in addressing the challenges posed by aggressive cancers like neuroblastoma, sarcomas (osteosarcoma, Ewing’s sarcoma), and malignant gliomas. By synergizing the anti-tumor effects of OV therapy with engineered NK cell therapeutics, preliminary studies suggest a substantial enhancement in anti-tumor activity. The approach offers a novel strategy to combat cancers with poor prognoses, potentially revolutionizing cancer treatment paradigms. The safety profile of the virus platform and the rapid translation of CAR-based therapies into clinical applications underscore the immediate human application potential of this technology. The technology is currently at the pre-clinical testing stage, with planned activities including in vivo synergy studies in murine models, cGMP production of the OV platform, biotox testing, and regulatory approvals for Phase I studies of the combination therapy. The technology presents licensing opportunities for companies involved in biopharmaceuticals, immunotherapy, and cancer treatment. Immediate applications include advancing the technology towards clinical trials, with the potential to revolutionize cancer treatment protocols. The intersection of OV therapy and cellular immunotherapy opens avenues for innovative product development and service offerings aimed at improving patient outcomes in oncology.

TS-003697 — This IP is a significant advancement in cancer therapy, specifically targeting neuroblastoma—a tumor commonly found in children. The innovative oncolytic virus has been engineered to improve immune recognition of neuroblastoma antigens while enhancing the body’s natural immune response. What sets this IP apart is its utilization of a chimeric HSV backbone, which allows for improved viral gene expression. By expressing the neuroblastoma antigen (Phox2B), the virus aims to improve native immune activity against the tumor, similar to its approach with EphA2 for other tumors. The virus is intended to work in tandem with an engineered CAR-T cell that recognizes the virus-expressed antigen, thereby increasing CAR-T and native T cell activity against the tumor. The potential applications of this technology are broad. As a standalone therapy, it offers a promising treatment option for patients with neuroblastoma. When used in combination with CAR-T therapy, it holds the potential to significantly enhance anti-tumor activity, addressing a critical need in pediatric oncology. The IP is entering proof of principle and pre-clinical testing stages at CHOP with collaborators.

TS-003696 — This IP is significant advancement in cancer therapy, specifically targeting neuroblastoma—a tumor commonly found in children. This innovative oncolytic virus has been engineered to improve immune recognition of neuroblastoma antigens while enhancing the body’s natural immune response. What sets this IP is its utilization of a chimeric HSV backbone, which allows for improved viral gene expression. By expressing the neuroblastoma antigen (Phox2B) along with human IFNγ, the virus aims to upregulate MHCI associated with Phox2B antigens, thereby enhancing T cell activity against the tumor. This approach not only boosts the efficacy of CAR-T therapy but also stimulates native T cell responses, ultimately enhancing immune-mediated anti-tumor activity. The potential applications of this technology are wide-ranging. As a standalone therapy, it offers a promising treatment option for patients with neuroblastoma. When used in combination with CAR-T therapy, it holds the potential to significantly enhance anti-tumor activity, addressing a critical need in pediatric oncology. The IP is entering pre-clinical testing, with plans to assess its efficacy in conjunction with CAR-T cells at CHOP.

TS-003695 — This IP is designed to combat neuroblastoma, a type of tumor commonly affecting children. It involves the development of an early generation oncolytic virus engineered to express a neuroblastoma antigen (Phox2B), thereby enhancing immune recognition of the tumor. This virus is intended to work synergistically with a specific engineered CAR-T cell designed to target the Phox2B-MHCI associated antigen. By harnessing the body’s immune system, the therapy aims to improve immune-mediated anti-tumor activity against neuroblastoma. One of the key advantages of this technology is its early generation ICP34.5 deletion virus backbone, which has been safely used in pediatric solid tumor clinical trials. This feature facilitates easier translation to clinical trials, particularly in pediatric settings, potentially streamlining the regulatory approval process. The potential applications of this technology are vast. As a standalone therapy, it offers a promising option for patients with neuroblastoma or tumors expressing the Phox2B antigen. When combined with engineered CAR-T therapy, it holds the potential to synergistically enhance anti-tumor activity, thus overcoming potential evasion mechanisms associated with CAR-T therapy. Further development of the IP involves pre-clinical testing in conjunction with CAR-T therapy using patient-derived xenograft models. Subsequent steps include cGMP production, IND approval, and potential clinical trials.

TS-003694 — This IP is a cutting-edge innovation engineered to combat neuroblastoma, a form of tumor primarily affecting children. This oncolytic virus, developed through an NIH U54 supplemental grant, targets tumor-associated antigens and harnessing the power of the immune system. The IP entails the creation of a sophisticated virus capable of expressing both a neuroblastoma antigen (Phox2B) and interferon gamma (IFN gamma). The Phox2B antigen aids in improving Major Histocompatibility Complex Class I (MHCI) upregulation, thereby enhancing immune recognition of the tumor. Additionally, the expression of IFN gamma further boosts MHCI expression in responsive tumors, augmenting both native T cell activity and engineered CAR-T cell response. One of the key advantages of this technology lies in its early generation ICP34.5 (-) backbone virus, which facilitates easier FDA approval due to prior clinical trial experience in pediatric settings. By leveraging this well-established backbone, the oncolytic virus offers a promising avenue for the treatment of neuroblastoma while minimizing regulatory hurdles. The potential applications of this innovative technology are multifaceted. As a standalone therapy, it is a compelling option for patients with neuroblastoma or tumors expressing the Phox2B antigen. When combined with engineered CAR-T therapy targeting the MHCI-associated antigen, the oncolytic virus holds the potential to synergistically enhance anti-tumor activity. Such combination therapy not only increases antigen density—thus overcoming potential CAR-T evasion mechanisms—but also leverages the early generation backbone for swift translation into clinical use. Further development of the IP involves pre-clinical testing in conjunction with CAR-T therapy. By partnering with collaborators and regulatory authorities, the goal is to advance this technology towards FDA approval and ultimately bring it to patients in need.

TS-003692 — This IP is an innovative approach to cancer treatment and involves genetically modified herpesviruses designed to selectively replicate within malignant cells, leading to their destruction. The virus expresses interleukin-15 (IL-15), a cytokine that enhances the cytotoxic activity of T and NK cells, further boosting the anti-tumor immune response. This technology offers significant advantages over existing methods. By improving the cytotoxic activity of immune cells, particularly T and NK cells, it enhances the body’s natural ability to target and destroy cancer cells. This could lead to more effective treatment outcomes, especially in cancers resistant to conventional therapies. The ability of the virus to modulate the tumor microenvironment makes it applicable across various cancer types. Unlike previous attempts with IL-15 expression in oHSV, this C134-based virus shows efficacy in murine models, potentially due to its ability to evade PKR-mediated antiviral translational arrest. This standout feature allows sustained IL-15 production during treatment, enhancing its therapeutic effects. Pharmaceutical companies specializing in immunotherapy and cellular therapy, as well as those focused on oncolytic virus-based treatments, are likely to be interested in licensing this technology for further development and commercialization. There may be opportunities for collaborations with cancer research institutions and clinics looking to advance novel treatment options. Further development of this technology involves preclinical IND-enabling studies to assess its safety and efficacy in preparation for clinical trials. Ongoing research aims to identify other cancers susceptible to treatment with this virus, characterize its immune-stimulating effects, and optimize dosing strategies to maximize therapeutic benefit while minimizing inflammatory responses.

TS-003691 — This IP is designed to target and treat cancers resistant to conventional therapies, and the technology involves genetically modified herpesviruses that selectively replicate within malignant cells, leading to their destruction. The virus triggers inflammatory responses and recruits immune cells, which converts an immune-unresponsive tumor into an immune-active environment. Notably, the oHSV expresses interleukin-12 (IL-12), a cytokine that enhances the activity of immune cells like T and NK cells, further boosting the anti-tumor immune response. The IP offers several advantages over existing methods. Firstly, it improves IL-12 production and extends the duration of immune activation, ultimately enhancing therapeutic effects against tumors. Secondly, it has shown promise in converting cold tumors into hot tumors, making them more susceptible to immune-mediated destruction. This versatility makes it applicable across various cancer types, including those that have shown resistance to other treatments. Compared to earlier generation IL-12 expressing oHSVs, this innovation demonstrates improved IL-12 production and activity in some models. Its ability to modulate immune cell function within the tumor microenvironment sets it apart from traditional cancer therapies. Further development of this technology involves characterizing the immune mechanisms underlying its response and exploring combination therapies to enhance its efficacy. Ongoing pre-clinical studies aim to investigate its compatibility with engineered cell therapies, such as CAR-T and CAR-NK cells, expanding its potential applications in adoptive cellular therapy. The IP stands to transform cancer treatment by providing a more targeted and effective therapy option, especially for patients who have failed conventional treatments. Pharmaceutical companies focusing on immunotherapy and cellular therapy, as well as those developing oncolytic virus-based treatments, are likely to be interested in licensing this technology for further development and commercialization.

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-000873 — The current timeframe required for current Good Manufacturing Product (cGMP) validation and approval is significant. The delay between development and approval is time intensive and the advancements that can improve treatment can be outdated by the time they reach the market. Genetic modifications would lead to restarting the production and approval process and delaying the introduction of the entry into human trials. Dr. Kevin Cassady and his team found that combinations of oncolytic viruses (OV) can be combined using current, approved cGMP stocks can be employed effectively and subsequently saving time that would have been spent on re-engineering, production, and validation, as well as the expense associated. The clinical outcome would be improved as this new process allows for a more rapid and cost-effective approach to clinical translation using existing stock of virus.