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Pancreatic cancer is the fourth most common cause of death from cancer in the U.S. The overall 5-year survival rate for this disease is 8.5%. Glypican-1 (GPC1), a cell surface heparan sulfate proteoglycan protein that is overexpressed in pancreatic cancer. Due to this preferential expression, GPC1 represents a potential candidate for targeted therapy for patients with pancreatic cancer and other GPC1 expressing cancers such as prostate cancer.

Neuroblastoma is a rare pediatric cancer with approximately 1,000 new cases arising annually. Current therapies have a less than forty-five percent (45%), three-year survival rate which demonstrate a need for a more effective treatment against this disease. Glypican-2 (GPC2) is a cell surface protein that is preferentially expressed in pediatric cancers including neuroblastoma, which makes GPC2 an attractive candidate for targeted therapy. 
 

Human papillomavirus (HPV) has been linked to many cancers including cervix, uterine, anus, vulva, vagina, and penis. Although HPV vaccines exist to prevent HPV-associated cancers, there are still more than 5,000 deaths caused by HPV-associated cancers each year in the US and cervical cancer continues to be the second leading cause of cancer death in women ages 20 to 39.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. standard treatment for HCC is not suitable for a large proportion of liver cancer patients. As a result, alternative treatments are needed. Chimeric antigen receptor (CAR) T cell therapy is a promising alternative approach selectively targets targeting tumors via tumor-specific antigens. However, to date, no effective CAR T cell therapy exists for HCC. 

CD276 (also called B7-H3) is a pan-cancer antigen expressed in multiple solid tumors and an emerging cancer target. CD276 protein is overexpressed in pancreatic cancer, prostate cancer, breast cancer, colon cancer, lung cancer, and brain tumors (such as neuroblastoma) – making it an ideal target for cancer therapy. 

Investigators at the National Cancer Institute (NCI) have isolated a panel of anti-CD276 single domain antibodies (also known as nanobodies) from novel camel and rabbit single domain (VHH) libraries by phage display. 

Mesothelin is a cell surface protein that is an excellent target for immunotherapy because of its limited expression on normal tissues and its high expression on many cancers, including mesothelioma, cholangiocarcinoma, pancreatic, ovarian, lung, stomach, bile duct, and triple-negative breast cancer.

This technology includes irradiated Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCL) as feeder cells for the ex vivo expansion of natural killer (NK) cells. EBV-LCL feeder cells, altered by radiation to prevent uncontrolled growth, provide a supportive environment for NK cells to multiply effectively. This method addresses the challenge of obtaining sufficient quantities of functionally active NK cells, which are crucial components of the immune system known for their ability to target and destroy tumor cells and virally infected cells.

This technology includes the method of blocking CD38 in expanded natural killer (NK) cell therapy in combination with daratumumab in patients with multiple myeloma. Our in vitro studies have already confirmed the addition of NK cells to myeloma cells that have been exposed to daratumumab enhances myeloma killing compared to single agent treatment.

This technology includes six human monoclonal antibodies (mAbs) that target tumor antigens derived from the CT-RCC HERV-E (human endogenous retrovirus type E) to generate Chimeric Antigen Receptor (CAR) T cells to treat patients with advanced clear cell renal cell carcinoma (ccRCC). These mAbs were identified from Adagene Inc’s human antibody phage library, and data show that majority of these mAbs only bind to CT-RCC HERV-E+ ccRCC cells, which express TM but not CT-RCC HERV-E non-expressing ccRCC cells nor non-RCC cells.

Summary

The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for a class of novel aplithianine-derived small molecule analogs that compete with ATP for binding on a range of clinically relevant kinases including: