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.
Mesothelin is a cell surface protein that is highly expressed in aggressive cancers, such as malignant mesothelioma, ovarian cancer and pancreatic cancer, lung cancer, breast cancer, cholangiocarcinoma, bile duct carcinoma and gastric cancer. Because of this selective expression, mesothelin is an excellent candidate for targeted therapeutics, such as monoclonal antibodies (mAbs) and chimeric molecules. Current anti-mesothelin therapeutic mAb candidates bind to an epitope in Region I of mesothelin. Unfortunately, Region I contains the interaction site MUC16/CA125, a mesothe
Neuroblastoma is a rare pediatric cancer that affects one in every hundred thousand children under the age of fifteen in the United States. Current standards of care are chemotherapy and surgery, followed by stem-cell treatments, radiation and anti-ganglioside antibody therapy, which yield an average three-year survival rate of 10-45%. This demonstrates a need for more effective therapies.
Bacterial spores can be modified to display molecules of interest, including drugs, immunogenic peptides, antibodies and other functional proteins of interest (such as enzymes). The resulting engineered bacterial spores can provide many useful functions such as the treatment of infections, use as an adjuvant for the delivery of vaccines, and the enzymatic degradation of environmental pollutants.
The National Cancer Institute seeks parties to license human monoclonal antibodies and immunoconjugates and co-develop, evaluate, and/or commercialize large-scale antibody production and hepatocellular carcinoma (HCC) xenograft mouse models. An advantage of these monoclonal antibodies as a potential therapeutic is their specificity, which would reduce deleterious side-effects. HCC is the most common form of liver cancer, and is among the more deadly cancers in the world. There is a need for new treatments that can be successfully applied to a large population of patients.
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.
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).
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.
Targeted toxins (e.g., immunotoxins) are therapeutics that have at least two important components: (1) a toxin domain that is capable of killing cells and (2) a targeting domain that is capable of selectively localizing the toxic domain to only those cells which should be killed. By selecting a targeting domain that binds only to certain diseased cells (e.g., a cell which only expresses a cell surface receptor when in a diseased state), targeted toxins can kill the diseased cells while allowing healthy, essential cells to survive.