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Human mesothelin is overexpressed by various cancers such as synovial sarcoma, mesothelioma, and ovarian, lung, esophageal, and gastric cancers. This selective expression on certain cancers suggests that mesothelin is an excellent target for anticancer therapeutics. However, a large fragment (“the shed portion”) of mesothelin is constantly shed from cells, and all current anti-mesothelin antibodies bind to the shed portion.

Patients receiving immunotoxin cancer therapy are less likely to experience the deleterious side-effects associated with non-discriminate therapies such as chemotherapy or radiation therapy. Unfortunately, the continued administration of immunotoxins often leads to a reduced patient response due to the formation of neutralizing antibodies against immunogenic epitopes contained within Pseudomonas exotoxin A (PE). 

Mesothelin is a cell surface protein that is highly expressed in aggressive cancers such as malignant mesothelioma, ovarian cancer, pancreatic cancer, lung cancer, breast cancer, cholangiocarcinoma, bile duct carcinoma and gastric cancer. As a result, mesothelin is an excellent candidate for tumor targeted immunotherapeutics. However, the antibodies against mesothelin that are available for clinical trials are of murine origin. These antibodies have the potential to elicit immune responses in patients, which may adversely affect the ability to provide patients with repeated doses.

The National Cancer Institute Laboratory of Molecular Biology seeks parties for collaborative research to co-develop and commercialize antibody drug/toxin conjugates as liver cancer therapy and diagnostics. 

Certain members of the cucurbitacin and Withanolide family have been identified that can sensitize some tumor cell lines to cell death (apoptosis) on subsequent exposure of the cells to pro-apoptotic receptor agonists (PARAS) of the TRAIL "death receptors". These PARAS include TRAIL itself, and agonist antibodies to two of its receptors death receptor-4 (DR4 or TRAIL-R1) and death receptor 5 (DR5, TRAIL-R2). 

Polo-like kinase 1 (Plk1) is a critical protein involved in regulation of mitosis, and aberrant expression of this kinase is found in various cancer types.  Inhibition of Plk1 is currently being pursued in pre-clinical drug development for novel anti-cancer therapeutics.  Plk1 contains an allosteric domain, known as the polo-box domain (PBD), that is responsible for localizing the kinase domain to mitotic structures through protein-protein interactions.  

The glycoprotein CD56, also known as a neural cell adhesion molecule (NCAM), plays an important role in normal physiological functions.  It is expressed in low levels in normal cells such as neurons, glia, skeletal muscle and natural killer cells.

The National Cancer Institute seeks parties to license fully human antibodies for CH2-based research materials.

Researchers at the National Cancer Institute (NCI) have developed an improved insect cell line, Tni-FNL, derived from the cabbage looper, Trichoplusia ni.  The Tni-FNL cell line is capable of high level expression of heterologous proteins using baculovirus-based expression systems.  When compared to commercially available cell lines used for the same purpose, the Tni-FNL cell line often outperforms those for protein expression.  These cells have a high growth rate and are capable of growth at a lower temperature.

Adoptive cell transfer (ACT) is a promising immunotherapeutic approach for cancer treatment. During ACT, if a patient is subjected to lymphodepletion prior to cell transfer, there is an observed improvement in a patient’s response to treatment. However, lymphodepletion is associated with detrimental effects, including severe immune dysfunction that persists after treatment.