Chronic leg ulcers are a debilitating vasculopathic complication for some patients with sickle cell disease (SCD). Prevalence of leg ulcers varies based on age and geographic location; about 5-10% of all SCD patients may suffer leg ulcers. These leg ulcers are painful, result in infections, hospitalization, disability, and negatively impact the patient’s social and psychological wellbeing on an ongoing basis.
Vaccines against non-viral cancers target mainly differentiation antigens, cancer testis antigens, and overexpressed antigens. One common feature to these antigens is their presence in central immunological tolerance. Using these vaccines, T cells underwent depletion of high avidity clones directed against such antigens. This depletion can cause the loss of T cells bearing high affinity T cell receptors (TCRs) for their cognate antigens which have superior cytotoxic capacity, longer persistence in the tumor microenvironment, and decreased susceptibility to immune suppression.
The development of an effective HIV vaccine has been an ongoing area of research. High variability in HIV-1 virus strains, however, represents a major challenge. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. Researchers at the National Cancer Institute (NCI) have developed a vaccine that overcomes these major hurdles by utilizing a strategy that identifies conserved regions of the virus and exploits them for use in a targeted therapy.
Steroid hormones have been implicated to play a fundamental role in the pathogenesis of prostate cancer. Polymorphisms in the genes that code for enzymes, or hormones involved in androgen regulatory pathway, reportedly influence risk for developing prostate cancer. Since many membrane transporters are modulators of steroid hormones absorption and tissue distribution, genetic polymorphisms in genes encoding these transporters may account for the risk of prostate cancer and the predicting of survival.
Inflammatory processes associated with the over-production of tumor necrosis-alpha (TNF-alpha), a potent activator of the immune system accompany numerous neurodegenerative diseases. TNF-alpha has been validated as a drug target with the development of the inhibitors Enbrel and Remicade (fusion antibodies) as prescription medications. Both, however, are large macromolecules that require direct injection and have limited brain access.
Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene are among the most common oncogenic drivers in human cancers, affecting nearly a third of all solid tumors. Point mutations in the KRAS gene most frequently affect amino acid position 12, resulting in the substitution of the native glycine (G) residue for other amino acids (e.g., aspartic acid (D), valine (V), cysteine (C) or arginine (R)).
Mantle cell lymphoma (MCL) is a group of aggressive B-cell lymphomas displaying heterogeneous outcomes after treatment. Some patients have the slowly progressing disease that does not require immediate treatment, while others have a disease that rapidly progresses despite highly aggressive treatment. A number of prognostic tools have been described to determine whether patients have slow or rapidly progressing diseases, including the mantle cell lymphoma International Prognostic Index (MIPI) and biomarkers, such as KI-67.
Tumor invasion and metastasis are the primary drivers of cancer-related mortality. Therapies that have an ability to specifically target invasive and/or metastatic cells are anticipated to have a significant impact in the clinical management of advanced cancers.
Researchers at the National Cancer Institute’s Biopharmaceutical Development Program recently developed massively parallel sequencing methods for virus-derived therapeutics such as viral vaccines and oncolytic immunotherapies.
This technology provides improved processes for production and purification of nucleic acid-containing compositions, such as non-naturally occurring viruses, for example, recombinant polioviruses that can be employed as oncolytic agents. Some of the improved processes relate to improved processes for producing viral DNA template.