TS-000913 — Peptides can be used to stimulate antigen-specific T cells, allowing activated T cells to be isolated from immune individuals to be used in vaccination or treatment in others. The novel disease Coronavirus, also denoted as 2019-nCoV, was recognized by the World Health Organization as an unknown etiology in December of 2019. Severe Acute Respiratory Syndrome (SARS) is a disease that presents flu-like symptoms that is caused by coronavirus (SARS-CoV). A current process widely applicable to many pathogens uses the Miltenyi Prodigy device. In a study led by Dr. Dean Lee, his team found that this process can be adapted to SARS-CoV-2 using a specialty mix of peptides to isolate T cell immunity.

TS-000912 — There are a few prominent diseases that affect the kidney, such as nephrotic syndrome and diabetic nephropathy. To treat Type II diabetes, there is a readily available pharmaceutical known as pioglitazone that is often used in conjuncture with other compounds to reduce proteinuria in patients with kidney diseases. A team of researchers at Nationwide Children’s Hospital have developed a novel compound to act as a treatment agent in cases of kidney disease. The new design has similar insulin sensitizing effects as pioglitazone as well as its ability to reduce proteinuria. This compound, titled GQ-16, has similar efficacy as traditional Type II diabetes drugs and acts as a new indication for nephrotic syndrome or kidney diseases, with a significant reduction in side effects such as weight gain or adipogenesis.

TS-000906 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. Additionally, CD38 presenting cells have been used as a marker for cancer stem cells, specifically those that often avoid recognition when common surface antigen processes are used. CARK1 is a phosphorylate that impacts cell growth and development. A team led by Dr. Dean Lee has developed CD38k0 NK cells that they combine with CARK1 to create a series of monoclonal antibodies that targets cancer cells. Along with better cell targeting, this combination improves the efficacy of treatment in comparison to the CAR, NK, or CD38 antibodies as independent components.

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 The delay between development and approval is time intensive and the advancements that can improve treatment can be outdated by the time they reach the market.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.

TS-000859 — Nephrotic syndrome (NS) is a common kidney disease found in children that creates an overabundance of protein in the urine, comparable to proteinuria in adults. As of now, there are no approved safe and effective treatment for NS, especially for those whose NS is steroid or multi-drug resistant. A team of researchers have identified a series of new molecular targets for future drug development. Using glomerular transcriptomes and informatic analysis, clinicians will be able to identify immunosuppressive approaches that are distinct from the current procedures.

TS-000857 — CD33 is a receptor that spans multiple membranes and is expressed on myeloid lineage cells and sometimes lymphoid cells. A team of researchers led by Dr. Dean Lee have found a new way to modify existing CD33 processes to provide Natural Killer (NK) cells the additional ability to recognize cell targets expressing CD33. Acute Myeloid Leukemia (AML) expresses multiple antigens, where CD33 is the most common. This new process, labeled as CD33-CAR, shows a significant advantage in targeting AML that presents with CD33, especially in cases that resist unmodified NK cells.

TS-000854 — Dr. Kevin Cassady and his team have identified an amino acid epitope encoded from Syndecan 4 (SDC4) that binds to a receptor protein on immunosuppressive myeloid and dendric cells called GPNMB. This group has developed a series of fusion proteins including FcGamma (Fcγ) fusions to encode the binding GPNMB-interacting domain, and shared antigens containing epitope tags. They have incorporated the fusion into virus expressed antigens to target myeloid cells in the tumor microenvironment in order to change their functional activity and enhance uptake and processing of antigens. Because SDC4 and GPNMB act as co-inhibitory molecules, they anticipate that fusion proteins will disrupt this interaction, which will enhance T cell activity and could be used as an anti-cancer immunotherapy.

TS-000842 — In gene expression studies from early oHSV clinical trials, it was found that the cytokine IL27 is a potential target for therapeutic optimization. The cytokine’s expression levels are observed to be directly related to the improvement of the patient survival following treatment that includes an oncolytic HSV. Early data collected by Dr. Kevin Cassady confirms that the virus-based expression correlates with improved survival, and reduced tumor cell growth and has cleared immune cells from the tumors as well.

TS-000841 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. In a group study it was found that by using TGFb-imprinting, NK cells are driven to a pro-inflammatory phenotype with hypersecretion of IFN-γ, TNF-α, and GM- CSF. These cells, now TGFbi, had decreased degrees of CD38 at both the RNA and the protein level. Studies performed by Drs. Dean Lee and Marcelo Pereira found that CD38 NK cells can be utilized to target CD38+ multiple myeloma patients and improve their progression-free survival by avoiding death of healthy surrounding cells, as well as enhancement of NK cell function.

TS-000834 — Cancer and their tumors create and thrive in a microenvironment that is highly immune suppressant. By targeting specific genes and genetically modifying natural killer (NK) cells, the clinical outcomes of cancer immunotherapy have the advanced ability to overcome these diseases. NK cells in solid tumors have been reported to exhibit an inactive and dysfunctional state, and expanded NK cells under hypoxic conditions showed a decrease in cytotoxic ability. Drs. Dean Lee and Marcelo Pereira found that by using the developed approach that focuses on Cas9/RNP, the HIF1a in NK cells can permanently overcome the effects of hypoxia without the noted disadvantages of small-molecule inhibitors.

TS-000738 — In all living cells, extracellular vesicles (EVs) are naturally produced. Drs. Kevin Cassady and Uksha Saini have developed a streamlined approach to utilize these EVs to deliver biologics and clinical drug treatments that permit repeated treatments without the possibility of limiting therapeutic delivery due to the natural immune response. This method produces an immune inert drug delivery system that, unless the EVs are designed to encode immunostimulatory molecules, should not invoke an immune response. Our preliminary studies show that we can load extracellular vesicles (EVs) with a therapeutic payload of our choice. Retroviruses co­opt and use much of the same pathways involved in cellular EV production for virus exit of the infected cell. We therefore hypothesized that Lentiviruses (a non-replicating retrovirus commonly used in the lab for gene expression) would provide a modifiable platform to generate therapeutic gene products that that would be preferentially transported and packaged into cellular EVs. This platform could then be modified and developed as a potential therapeutic delivery platform.

TS-000737 — Nephrotic syndrome (NS) is a common kidney disease found in children that creates an overabundance of protein in the urine, comparable to proteinuria in adults. As of now, there are no approved safe and effective treatment for NS, especially for those whom NS is steroid or multi-drug resistant. Current treatments for NS are only partially effective and often create notable toxicity, but existing thiazolidinediones (TZDs) used for proteinuria in adults have resulted in reduction of proteins found in the urine. Introducing the TZD pioglitazone (PIO) to a trial study conducted by Dr. William Smoyer, pediatric patients with multi-drug resistant NS showed notable proteinuria reduction in comparable time periods, both before and after the addition of PIO in their medical regimens.

TS-000556 — Oncolytic viruses (OVs) target cancer cells, killing them from the inside. As the contaminated cancer cells die, the biproducts develop additional infectious components that continue to destroy the tumor. Dr. Kevin Cassady and his team have found that using OV-based “shared” antigen expression allows the immune system to recognize these antigens and improves the capacity of the immune system to fight tumor activity. Shared antigen expression includes proteins that are overexpressed by many tumors. They have been able to construct additional OVs that improve the immune targeting glioma and its associated antigen, IL13Ra2. This group is simultaneously investigating other ways enhance the anti-glioma activity by combining OVs with Chimeric Antigen Receptor-targeted T cells directed against IL13Ra2. In pre-clinical trials, this combination has produced improved anti-tumor activity with lower doses and safe to the patient.

TS-000446 — Airway epithelial cells (AECs) in the lungs play a crucial role in maintaining a conduit for air and defend against pathogens. Various acute and chronic pulmonary diseases damage AECs resulting in their altered structure and function. However, the AEC renewal is a slow process. Researchers at Nationwide Children’s Hospital have generated Airway Epithelial Stem cells using gene editing technology that will provide unlimited cell source for AECs. Notably, these cells evade immune rejection in recipients. This preclinical invention may provide “off-the-shelf” product paving the way to regenerative respiratory therapeutics.

TS-000406 — Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas of neural origin. The only known curative therapy is complete resection. Researchers at Nationwide Children’s Hospital have screened two novel compounds (Didesmethylrocaglamide and Rocaglamide) that are easy to synthesize owing to their compact structure and low molecular weight. These drugs show anti-tumor activity with no overt toxicity in murine model. This preclinical invention is a promising treatment for MPNST and other tumors.

TS-000387 — Oncolytic viruses infect and replicate in tumor cells without harming normal tissue. Researchers at Nationwide Children’s Hospital have genetically engineered sophisticated ‘Herpes Simplex Viruses’ (HSVs) that express tumor associated antigens. These HSVs have elicited superior antitumor immune response against tumors in preclinical mouse models. These next generation HSVs are a valuable therapeutic option for controlling cancers.

TS-000132 — Mutation of the RSV NS1/2 proteins to attenuate the virus and boost immunogenicity