Cancer is the second leading cause of death worldwide. The primary cause of mortality from cancer is metastasis. While the underlying mechanisms of cancer metastasis are still being unraveled, the gp78 protein involved in ER-associated degradation (ERAD) appears to play a role in metastasis in sarcoma. Targeting gp78 may be a therapeutic option in cancer treatment.
Interleukin-15 (IL-15) and IL-21 have been reported to support the function of anti-tumor T cells. However, their use in the clinic has been constrained, in part, by dose-limiting toxicity and the need for repeated administration. To overcome these limitations, researchers in the National Cancer Institute (NCI) Experimental Transplantation and Immunology Branch (ETIB) have developed synthetic IL-15 and IL-21 molecules for autocrine expression by the engineered therapeutic T cel
Primary liver tumors and secondary hepatic malignancies are among the leading causes of cancer-related deaths. Liver metastases account for 95% of all hepatic cancers, and the liver is the most common site for organ metastasis in the body. The gut microbiome serves an important role in antitumor immunity regulating the efficacy of chemo- and immunotherapies. The liver is exposed to gut bacteria through blood from the intestine, with 70% of the whole liver’s blood supply coming from intestinal blood. Changes in the commensal microbiome may affect immune cell function in the liver.
Epidermal growth factor receptor (EGFR) is a transmembrane protein involved in cell growth and proliferation. Mutations in this protein can lead to overexpression, causing several types of cancer; notably, non-small cell lung cancer (NSCLC). For example, mutations in EGFR are found in up to 50% of NSCLC patients and the E746-A750 deletion accounts for 30-40% of such EGFR mutations. Currently, there are no available therapeutics that specifically target the E746-A750 deletion.
Bone-loss-related diseases, such as periodontitis, are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. There are several signaling pathways that participate in the osteoclastogenesis process. Finding inhibitors of these pathways and other osteoclastogenesis-related pathways may have an effect on bone-loss diseases.
Human papillomavirus (HPV) has been associated with the cause of several cancer types, including cervical, anal, and head and neck cancers. There has been great success in preventing HPV infections with the development of prophylactic HPV vaccines, Gardasil and Cervarix. However, these vaccines have only been shown to prevent HPV infection and not treat those already infected with HPV. These vaccines elicit antibody responses to late HPV genes, and thus would not be effective in treating established tumors.
There are no analgesics to ameliorate chronic pain without adverse side-effects (e.g., respiratory depression, gastrointestinal effects, tolerance, dependence), thus forcing patients into a difficult choice of negative impacts on quality of life. Most of the analgesics used for chronic and acute pain are drugs such as oxycodone, morphine, oxymorphone, and codeine. All of these opioids have been subject to misuse; prescription drug abuse is a severe problem worldwide, causing high mortality and greatly increased emergency room visits.
Several Fibroblast Growth Factor Receptor 4 (FGFR4) specific antibodies with binding affinity at the nanomolar range have been successfully developed at the Genetics Branch. These antibodies have been made into different formats of therapeutic including Antibody Drug Conjugate (ADC), Bispecific T cell engager (BiTE) ae well as Chimeric Antigen Receptor (CAR)-T cells.
Proof of principle experiments have shown that when treated with FGFR4 positive tumor cells:
A significant challenge in developing therapies for the treatment and prevention of cancer has been the discovery, selection, and exploitation of antigens.
Degeneration of retinal tissues occurs in many ocular disorders resulting in the loss of vision. Dysfunction and/or loss of Retinal Pigment Epithelium Cells (RPE) and disruption of the associated blood retinal barrier (BRB) tissue structures are linked with many ocular diseases and conditions including: age-related macular degeneration (AMD), Best disease, and retinitis pigmentosa. Engineered tissue structures that are able to replicate the function of lost BRB structures may restore lost vision and provide insight into new treatments and mechanisms of the underlying conditions.