Improved PE-based Targeted Toxins: A Therapeutic with Increased Effectiveness

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.

High Affinity Monoclonal Antibodies Targeting Glypican-2 for Treating Childhood Cancers

Neuroblastoma is a rare pediatric cancer with approximately 1,000 new cases arising annually. Current therapies have a less than forty-five percent (45%), three-year survival rate which demonstrate a need for a more effective treatment against this disease. Glypican-2 (GPC2) is a cell surface protein that is preferentially expressed in pediatric cancers including neuroblastoma, which makes GPC2 an attractive candidate for targeted therapy. 
 

Human Monoclonal Antibodies Targeting Glypican-2 in Neuroblastoma

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.

Software for Modeling Delivery and Penetration of Antibody Conjugates

The National Cancer Institute (NCI) seeks parties to license software for modeling the targeted delivery of anti-cancer agents in solid tumors.

The software models the permeability and concentration of intravenously administered antibody anti-cancer agent conjugates in solid tumors.  The models can be used to determine optimal dosing regimen of a therapeutic in a particular cancer type.  Thirty factors that affect delivery rates and efficiencies are analyzed as variables in generating the models.

Synthetic Bacterial Nanoparticles as Drug and Vaccine Delivery Vehicles

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.

High Affinity Nanobodies Targeting B7-H3 (CD276) for Treating Solid Tumors

CD276 (also called B7-H3) is a pan-cancer antigen expressed in multiple solid tumors and an emerging cancer target. CD276 protein is overexpressed in pancreatic cancer, prostate cancer, breast cancer, colon cancer, lung cancer, and brain tumors (such as neuroblastoma) – making it an ideal target for cancer therapy. 

Investigators at the National Cancer Institute (NCI) have isolated a panel of anti-CD276 single domain antibodies (also known as nanobodies) from novel camel and rabbit single domain (VHH) libraries by phage display. 

Chimeric Antigen Receptors (CAR)-T Cells that Target the Non-Shed Portion of Mesothelin as a Therapeutic Agent

Mesothelin (MSLN) is an excellent target for antibody-based therapies of cancer because of its high expression in many malignancies but lack of expression on essential normal tissues. Unfortunately, a large fragment of MSLN is shed from cancer cells, causing the currently available anti-MSLN antibodies (and immunoconjugates thereof) which bind to the shed portion of MSLN to quickly lose their therapeutic effectiveness over time. Indeed, the shed portion of MSLN can act as a decoy for these antibodies, further limiting them from reaching and destroying tumor cells.

Single-domain monoclonal antibodies for the treatment of hepatocellular carcinoma

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.