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Human leukocyte antigen (HLA) LOH (LOH) is a known resistance mechanism by which cancers evade T cell receptor-(TCR-)based immunotherapies. This class of therapies includes immune checkpoint inhibition (ICI, e.g., Pembrolizumab), engineered TCR (T cell receptor)-T cell adoptive transfer, tumor infiltrating lymphocytes (TIL), T-cell engagers, and other modalities. Dozens of therapies in this category were developed with many in clinical trials. The resistance mechanism noted here, HLA LOH, causes these therapies to fail.

Cell culture investigations using spheroids and organoid models have had a major impact on biomedical advancement as alternative sources for costly, in vivo animal testing.  However, these 3-D cell constructs are limited in that they do not integrate extracellular components within the structure important for more reliable and accurate biological responses.  Extracellular matrix (ECM) from decellularized tissues provide a physical scaffolding and offers crucial biochemical and biomechanical cues for cellular constituents.

Despite recent breakthroughs in cancer immunotherapy, T-cell based therapies achieve limited efficacy in solid tumors. Immunosuppression, antigen escape and physical barriers to entry into solid tumors are issues faced. Identifying regulators in T-cell dysfunction remains challenging due to limitations of current screening platforms. 

Melanoma is an aggressive form of skin cancer that commonly becomes metastatic, spreading to nearby tissue or other parts of the body, including distant skin or subcutaneous sites such as the lungs, liver, brain, or bone. Metastatic melanoma is very drug resistant and difficult to treat, and therefore, the prognosis for these patients is poor. There is a need for effective therapies for aggressive melanoma and other drug-resistant solid cancers. 

Human papillomavirus (HPV) is a group of human viruses known to cause various malignancies. Of the group, HPV-16 is the most prevalent strain – an estimated 90% of adults have been exposed. HPV-16 is also the strain most commonly associated with malignancy, causing the vast majority of cervical, anal, vaginal, vulvar, and penile cancers. Currently, HPV-positive malignancies non-responsive to surgery or radiation are incurable and poorly palliated by existing systemic therapies. Thus, an alternative therapeutic approach for HPV-positive malignancies is needed. 

Synovial sarcoma is a cancer affecting mesenchymal cells in connective tissues. This rare cancer is typically linked to genetic abnormalities or exposure to radiation. Metastatic growth throughout the body can occur primarily through blood circulation. More than 90% of synovial sarcomas show a characteristic t(X;18)(p11;q11) translocation involving the SYT and SSX genes. The resulting SYT-SSX abnormal fusion protein causes misregulation of downstream gene expression, leading to tumor formation.

CD22 is a protein expressed by normal B cells and B-lymphoid malignancies. Its limited tissue expression pattern makes it a safe antigen for targeted therapies, such as T-cell Receptor (TCR)-T cell therapy. CD22-targeting therapies already on the market, mainly antibody-immunotoxin conjugates and chimeric antigen receptors (CAR)-T cells, have limitations such as resistance to treatment and/or side effects. Resistance mechanisms to the current CD22 therapies involve loss or modulation of target antigen on the cell surface.

Over 34 million Americans are living with diabetes. An estimated 6.5 million Americans are living with Alzheimer’s disease (AD) and type 2 diabetes mellites (T2DM). Amyloidosis due to aggregation of amyloid-β is key pathogenic event in AD, whereas aggregation of mature islet amyloid polypeptide (IAPP37) in human islet leads to β-cell dysfunction. A hallmark feature of T2DM is the accumulation of islet amyloid polypeptide fibrils in pancreatic islets. Such accumulations form amyloid plaques and cause apoptosis of -cells of islets. 

Nuclear medicine is the second largest source of medical radiation exposure to the general population after computed tomography imaging. Imaging modalities utilizing nuclear medicine produce a more detailed view of internal structure and function and are most commonly used to diagnose diseases such as heart disease, Alzheimer’s and brain disorders. They are used to visualize tumors, abscesses due to infection or abnormalities in abdominal organs.

• Topoisomerase 3B (TOP3B) is the only topoisomerase that can act on RNA as well as DNA. Thus, it is a target of interest for the development of cancer therapies and RNA viral infection therapies. TOP3B is not an essential gene for carcinogenesis, but a subset of cancer cells with pre-existing genome instability are particularly vulnerable to the inactivation of TOP3B. While inhibitors for other topoisomerases are among the most potent and widely used anticancer agents, there are no known inhibitors of TOP3B.