Retinal degeneration is a deteriorative condition of the human retina caused by the progressive and eventual death of photoreceptor cells. To date, no effective treatment for genetically inherited or age-associated retinal degeneration, which includes a large patient population worldwide, is available.
Molecular profiling with high throughput assays has gained utility in the management of select cancer patients and several gene expression-based assays are now marketed for improved prognostic accuracy for patients with cancer.
Papillomavirus pseudoviruses that comprise the L1/L2 capsid proteins can package a wide variety of non-viral DNA plasmids and deliver the packaged genetic material to cells. This function makes them attractive candidates as targeted gene delivery vehicles.
Vascular Endothelial Growth Factor-A (VEGF-A) is an angiogenic agent that drives blood vessel formation in solid tumors and other diseases, such as macular degeneration and diabetic retinopathy. Several therapies that target the ability of VEGF to stimulate angiogenesis have been approved. These therapies regulate VEGF-A activity by binding VEGF-A, thereby blocking VEGF-A from binding to its receptor on target cells. This technology utilizes a different approach to regulating VEGF-A activity by providing a VEGF-A protein antagonist that is produced by engineering native VEGF-A protein.
T cell immunotherapy is used in the treatment of various pathologies – including cancers and infections. Current therapies employ chimeric antigen receptors (CARs) consisting of the intracellular fragment of CD3-zeta as the signaling domain with varied combinations of co-stimulatory, transmembrane, spacer/hinge, and extracellular targeting domains. While effective in treating hematological malignancies, CAR T cells need to be activated through T cell receptor (TCR) activation.
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:
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.
Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) developed an MRI-method that is based on the acquisition of multiple pulsed field gradient (m-PFG) rather than single-pulsed field gradient (s-PFG) MRI sequences. In particular, double PFG (dPFG) MRI sequences offer higher sensitivity and greater robustness, as they are more sensitive to the effects of “restriction;” i.e., to water trapped within the axon’s intracellular space, and thus to the diameter of the axons.
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 (IL)-34 is a homodimer that is produced mainly by keratinocytes, neuronal cells and regulatory T cells (Tregs). It is believed to play important roles in chronic inflammation and the homeostasis of microglia. Currently, there is no effective treatment for many types of retinal degeneration. An improved treatment of autoimmune uveitis is also needed, as current uveitis treatment primarily uses steroidal anti-inflammation medication, which may produce significant unwanted side effects in long-term use.