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.
Neuroblastomas are the most common extracranial solid tumors in pediatric patients, with 700-800 new cases annually in the United States. Metastatic neuroblastomas have a five-year survival rate of 50% and account for 15% of all pediatric cancer deaths. As such, more effective treatments against high-risk neuroblastomas are urgently needed.
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.
Recombinant immunotoxins (RITs) constitute a promising solution to hematologic cancers (e.g., Multiple Myeloma [MM]). RITs are chimeric proteins composed of a targeting domain fused to a bacterial toxin. Upon binding to a cancer cell displaying the target antigen, RITs are internalized, metabolized and the released toxin kills the cell. While highly active and effective, current RITs have short half-lives, requiring them to be used in high concentrations for treatment. At such high concentrations, RITs may show nonspecific activity and kill healthy cells.
Researchers at the National Eye Institute (NEI) have discovered an invention describing a composition and method(s) of using such composition for preserving viability of cells, tissues, or organs at a low temperature (around 4ºC). Current cold storage solutions or methods for cells, tissues, and organs are suboptimal due to irreversible damage to cold-sensitive tissue or organ transplants that need a longer term of storage for facilitating clinical practices.