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This technology includes a family of small-molecule antagonists that selectively block the 5-HT_2B serotonin receptor—an upstream driver of tissue-remodeling—to address fibrotic, cardiopulmonary and related disorders. Built on a conformationally-locked “(N)-methanocarba” nucleoside scaffold, the compounds show nanomolar potency, >30–400-fold selectivity over the closely related 5-HT_2C receptor, and favorable oral bioavailability in rodents.

Immortalization of plasma cells leads to Multiple Myeloma (MM). Signaling Lymphocyte Activation Molecule F7 (SLAMF7) is highly expressed on the malignant plasma cells that constitute Multiple Myeloma. The expression of SLAMF7 by MM cells and lack of expression on nonhematologic cells makes SLAMF7 a promising target for chimeric antigen receptor (CAR) T cell therapies for the treatment of MM. 

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.

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.

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. 

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.