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.

TS-002301 — CD38 regulates the metabolism and the immunomodulation of tumor microenvironments, making it an essential component to anti-cancer therapies. Researchers at Nationwide Children’s Hospital developed a novel technology using CD38 as a new insertion site for NK and T cells. They generated CAR-NK and CAR-T cells by integrating the DNA encoding CAR in the CD38 locus to enhance anti-tumor activity and improve metabolic function of NK and T cells. Additionally, this can be used in combination with CD38 monoclonal antibodies without risking fratricide.

TS-002300 — Hematologic cancers like leukemia, lymphoma and myeloma are found in 10% of adult cancer cases and 25% in pediatric cancer cases. Researchers at Nationwide Children’s Hospital’s Center for Childhood Cancer have developed a novel single-chain variable fragment (scFv) that targets and binds to CD38. The scFv can generate CD38 binding proteins, including chimeric antigen receptors (CAR), single-chain antibodies, multi-specific engagers, etc. Additionally, the single-chain variable fragments can be incorporated into polyfunctional proteins and have identical binding properties as CD38 antibodies which are used as anti-cancer therapeutics.

TS-002167 — Research links increased expression of neuregulin-1 (NRG1) to neurological disorders (schizophrenia, bipolar disorder, autism spectrum disorder, epilepsy, etc.), cancers (breast, prostate, lung, gastric cancers), metabolic syndrome and multiple sclerosis. Researchers at Nationwide Children’s Hospital developed a treatment to manipulate mammalian gene expression with bacterial extracellular vesicles. This treatment based on outer membrane vesicles (OMV) modulates expression of NRG1 by using porphyromonas gingivalis (Pg) tRNA and NRG1 mRNA to reduce NRG1 translation. Pg and closely related pathogens produce OMVs that contain proteins, lipids, nucleic acids and cytosolic compounds. Through metagenomic sequencing, researchers found that Pg OMVs contain tRNA that complements mammalian NRG1 mRNA. They also found that the tRNA can potentially stop the translation of NRG1. This complementation indicates a direct interaction between Pg tRNA and NRG1 mRNA which results in the reduction of NRG1.

TS-002166 — Education and awareness about mental health increased the demand for better digital programs so health care professionals can reach patients outside the clinical setting. Researchers at Nationwide Children’s Hospital created a program that sends multimedia text messages to encourage positive thinking and to reduce chances of readmission to behavioral health hospitals.

TS-002165 — Children have higher self-esteem when their needs are supported, which includes hair care. In 2020, staff members reported their knowledge gaps and lack of confidence and supplies regarding patient hair care. As a result, the Hair Care Equity Project was created at Nationwide Children’s Hospital to combat these challenges and to create a more inclusive environment for patients through education and product research. The Hair Care Equity Committee worked with vendors and dermatologists to carefully select products for trials and final selection. Now, staff members can access and order supplies for patients with all hair types.

TS-002164 — Congenital heart defects (CHD) are the most common birth defects with an occurrence rate of 1 in every 110 births. When transferring from pediatric to adult care, one-third of adolescents are in optimal cardiovascular health. Due to this, health behavior intervention is ideal in adolescence. This is especially crucial when youths report using e-cigarettes or the possibility of using one in the future. Researcher, Kristen Fox, at Nationwide Children’s Hospital created a tailored mHealth Vaping Prevention program for adolescents with CHD to reduce engagement with health risk behaviors. The curriculum is improved with added topics surrounding stress management and disease knowledge with the implementation of gamification and animations to facilitate knowledge and sustain engagement about tobacco product education.

TS-002163 — Researchers and professionals beginning their careers in pediatrics and/or rare disease clinical research sites may feel overwhelmed in the face of innovation, new territories and lifechanging research. A team of Certified Clinical Research Professionals at Nationwide Children’s Hospital created three additional modules for the Clinical Research Onboarding Program – The Survival Guide and an opportunity to access a Gene Therapy Immersion Program. Through this reference manual, the team hopes to share lessons and provide guidance on working in pediatrics clinical research for all learners.

TS-002162 — Dr. Jonathon Gisser, a pediatric gastroenterologist at Nationwide Children’s Hospital, researched and created a process called Gastric Secretion Reinfusion (GSR) to help salvage gastric fluids by reinfusing them into the jejunum. Gastrojejunostomy (GJ) tubes cause increased vomiting and/or gastric drainage in patients due to gastric outlet obstruction. The small intestine needs gastric fluids to prevent dehydration, dysmotility, malabsorption, malnutrition, electrolyte imbalances and increased gastric output because they are rich in electrolytes, enzymes and hormones. Currently, gastric fluids are typically discarded and replaced by nutrient-impoverished, exogenous fluids like intravenous fluids (IV). By implementing the Gastric Secretion Reinfusion technique, patients will experience decreased incidences of electrolyte abnormalities, vomiting and reliance on parenteral access and Total Parenteral Nutrition (TPN). Additionally, they will also experience an increase in tolerance of jejunal feeds and improved nutrition.

TS-002160 — Dysphagia affects 300,000 to 700,000 Americans every year. Individuals of any age can suffer with dysphagia which increases the demand for education and information. Providers working with individuals with dysphagia require easy, quick access to education and information regarding implementing the International Dysphagia Diet Standardization Initiative (IDDSI). Clinicians at Nationwide Children’s Hospital created the IDDSI Implementation Manual and Education. The manual provides healthcare providers with specific implementation steps, instructions and details to guide teams to successfully integrate IDDSI in their healthcare organization quickly along with additional supplemental educational materials.

TS-002159 — Currently, there is no standard protocol for observing patient readiness for recreational therapy. Inventors at Nationwide Children’s Hospital created the Therapeutic Recreation (TR) Leisure Engagement tool to document and assess the needs of patients with developmental or physical disabilities to promote well-being and recovery. Through this technology, therapeutic recreation specialists will further help patients by measuring their readiness for sessions, emotional presentation and social functions while providing leisure education.

TS-001983 — A research team at Nationwide Children’s Hospital developed a new therapeutic approach for delaying lower grade glioma malignant progression using adolescents and young adult models of glioma. The innovative approach uses autologous bone marrow isolated myeloid cells (GEMys) for the stable expression and secretion of interleukin 2 (IL2), a cytokine associated with responding to invading pathogens and the recruitment of cytotoxic anti-cancer immune cells to the tumor microenvironment (TME). These bone marrow derived GEMys can also be used to deliver other cytokines to potentiate the trafficking and activation of cytotoxic T and NK cells to kill tumor cells and reprogram the TME to prevent glioma progression. This novel innate immunotherapy is delivered systemically through intravenous injection and may be less toxic than chemotherapies.

TS-001178 — Currently there are few existing methods on coronary flow pattern automation. The DECFA platform fulfills this unmet need by predicting diseased coronary blood flow by integrating previously unutilized data features from (sonographic) Doppler echocardiography measurements, cardiac functional and other physiological data (e.g. heart rate, body weight, etc) using machine learning. The DECFA program is superior to manual intervention as it provides more efficient analysis, more accurately, and can accept raw video files of PW Doppler and Color Doppler B-mode files, applicable on mouse models, potentially applicable to humans. DECFA can analyze raw PW Doppler AND Color Doppler B-Mode AVI video files to calculate overall coronary blood flow and coronary flow reserve, and the separation of each coronary flow pattern into 4 distinct phases representative of the stages in a cardiac cycle. Benefits: More efficient analysis over manual intervention, less error than manual intervention, capable of accepting raw video files of PW Doppler and Color Doppler B-mode files, applicable on mouse models, potentially applicable to humans (not yet validated). New features include the analysis of raw PW Doppler AND Color Doppler B-Mode AVI video files to calculate overall coronary blood flow and coronary flow reserve, and the separation of each coronary flow pattern into distinct phases representative of the stages in a cardiac cycle. The machine learning aspect brings state-of-the-art technology to determine whether it may be useful in directly predicting/diagnosing coronary microvascular disease. Stage of Development: We are currently in the final stages of completing the data analysis for all of the in vivo coronary and cardiac physiological parameters that will be used to perform the final runs through the machine learning process. We did perform an “interim” analysis using about half of the data, the results of which were promising (inconclusive at this point, but they put the predictive value of coronary flow patterns above 90% for identifying diseased coronary blood flow). This process also uses the whole envelope instead of discrete points of the coronary flow pattern, in addition to the texture-analysis extension. After this process is complete in mice, we plan to obtain human coronary blood flow patterns to determine whether this could be clinically useful beyond research applications. Potential Applications/Markets: Our program could be utilized in a research setting for robust, comprehensive, and more efficient analysis of coronary flow patterns in mice measured through Doppler Echocardiography (It solves the problem of large inter/intra observer error and time required for manual analysis). The program could also be used clinically for use in the medical field for the same analysis if adjusted for human use. It could also be used as an add on feature to the VisualSonics Vevo 2100 software for added capabilities in analyzing PW Doppler coronary flow patterns and Color Doppler B-mode files. The parameters that we identify in our program could be potentially useful in clinical diagnostics/machine learning/prediction modeling for better identifying and predicting disease. Furthermore, we envision that this could be tested and applied to clinical coronary Doppler echocardiograms, with the readout being predictability of coronary microvascular disease based on the machine learning algorithm of coronary flow patterns. Opportunity/Seeking: Development Partner Commercial Partner Licensing IP Status: Know-how based Copyright

TS-000972 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. When an NK cell is deficient or dysfunctional, the efficiency of the NK cells is severely limited. VISTA is a protein sequence that activates T cells and acts as a moderator for the immune system. It has low-to-moderate expression but has been the target of study by a team of researchers at Nationwide Children’s Hospital led by Dr. Dean Lee. By removing VISTA in expanded NK cells, the inhibitory signal will be eliminated and thus resulting in an enhanced ability of NK cells to target cancers and overcome the immune-suppressive signals for improved cancer immunotherapy.

TS-000969 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. Chimeric Antigen Receptor T cells (CAR T) are comprised of an extracellular antigen recognition domain, intracellular T cell activation and co-stimulatory domains. These cells allow for potent and specific targeting of cancer cells, bypassing the need for antigen presentation and T cell receptor recognition. Generating CAR T cells using the process of lentiviral transduction has limitations stemming from the random integration of transgenesis, where oncogene activation, gene silencing, or negative effects on the CAR T antitumor efficacy are possible.

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-000878 — Chimeric Antigen Receptor T cells (CAR T) are comprised of an extracellular antigen recognition domain, intracellular T cell activation and co-stimulatory domains. These cells allow for potent and specific targeting of cancer cells, bypassing the need for antigen presentation and T cell receptor recognition. CAR T is mostly generated using lentiviral transduction of autologous T cells in conjunction with non-specific expansion in cell culture. CAR T-specific stimulation has been described using genetically engineered artificial antigen presenting cells (aAPCs). A strategy designed by Dr. Dean Lee and his team can select and expand any CAR T cell product in culture. This allows for safely infused exosomes and other membrane particles derived from aAPCs to also be envisioned as a pharmacologic, given to patients receiving CAR T to promote in vivo expansion and persistence of said cells. This approach could also be applied to antigen-specific TCR stimulation by modifying the aAPC to express the appropriate MCH-peptide as the antigen.

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.