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The COVID-19 pandemic is a worldwide public health crisis with over 100 million confirmed cases and 2.4 million deaths as of February 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. Almost all the neutralizing antibodies targeting SARS-CoV-2 that are in development recognize the receptor binding domain (RBD) on the spike (S) protein. Blocking the interaction of RBD and the ACE2 receptor on human cells is the first of the two critical steps for neutralization of the virus.

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:

Chimeric antigen receptors (CARs) are hybrid proteins that consist of two major components: a targeting domain and a signaling domain.  The targeting domain allows T cells which express the CAR to selectively recognize and bind to diseased cells that express a particular protein.  Once the diseased cell is bound by the targeting domain of the CAR, the signaling domain of the CAR activates the T cell, thereby allowing it to kill the diseased cell.  This is a promising new therapeutic approach known as adoptive cell therapy (ACT).

Immortalization of plasma cells leads to plasma cell malignancy diseases such as multiple myeloma (MM). B-cell maturation antigen (BCMA) is a protein that is preferentially expressed by malignant and normal B cells and plasma cells, butnot on other cells in the body. This limited expression profile suggests that BCMA is a promising target for anticancer therapeutics for cancers in which there is excess production of plasma cells and B cells. 

Lassa Hemorrhagic Fever (LHF) is a serious disease caused by infection with Lassa virus (LASV) – highly prevalent in West Africa and spreading globally. LASV is associated with high morbidity and mortality rates, annually infecting 100,000 to 300,000 individuals and causing 5,000 deaths. Developing prophylactics and treatment for LASV is difficult due to challenges in inducing neutralizing antibodies and producing their target, the LASV glycoprotein trimer (GPC).

Adoptive cell therapy (ACT) is an attractive new therapeutic approach for treating various cancers. ACT has recently demonstrated a high degree of efficacy when treating patients with hematological malignancies. However, to date, no effective Chimeric Antigen Receptors (CAR) T cell therapy exists for solid tumors.