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-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-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-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-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.