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.
This technology includes antibodies for TMC1 protein as a treatment for hearing loss. TMC1 is one of the common genes causing hereditary hearing loss. Our laboratory used synthetic peptides corresponding to the TMC1 protein to immunize rabbits. The resulting antisera were shown to bind to TMC1 protein expressed in heterologous expression systems. TMC1 protein is required for the transduction of sound into electrical impulses in inner ear sensory cells.
This technology includes a small molecule drug (VDAC inhibitor, also known as VBIT4) that may be useful for inhibiting lupus disease. To test lupus animal model, VBIT4 was continuously administered for 5 weeks to mice and there was no mortality or clinical symptoms in these animals. Additionally, VBIT4 treatment blocked the development of skin lesions and alopecia of the ears and face, and suppressed the thickening of the epidermis that accompanies leukocyte infiltration.
Human cancers contain genetic mutations that are unique to each patient. Some of the mutated peptides are immunogenic, can be recognized by T cells, and therefore, may serve as therapeutic targets.
The National Institute on Drug Abuse (NIDA) is seeking interested parties to license or co-develop GDNFOS peptides and non-coding RNAs as therapeutic agents for neurodegenerative diseases.