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.
T cells currently employed for T cell-based immunotherapies are often senescent, terminally differentiated cells with poor proliferative and survival capacity. Recently, however, scientists at the National Cancer Institute (NCI) identified and characterized a new human memory T cell population with stem cell-like properties. Since these T cells have limited quantities in vivo, the scientists have developed methods by which high numbers of these cells can be generated ex vivo for use in T cell-based immunotherapies.
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.
Many biological and clinical procedures require functional validation of a desired cell type. Current techniques to validate rely on various assays and methods, such as staining with dyes, antibodies, and nucleic acid probes, to assess stem cell health, death, proliferation, and functionality. These techniques potentially destroy stem cells and risk contaminating cells and cultures by exposing them to the environment; they are low-throughput and difficult to scale-up.
The retinal pigment epithelium (RPE) is a cell monolayer with specialized functions crucial to maintaining the metabolic environment and chemistry of the sub-retinal and choroidal layers in the eye. Damage or disease causing RPE cell loss leads to progressive photoreceptor damage and impaired vision. Loss of RPE is observed in many of the most prevalent cases of vision loss, including age related macular degeneration (AMD) and Best disease.
The HIV-positive population continues to rise despite a worldwide decline in the rates of infection caused by human immunodeficiency virus (HIV). The HIV virus continues to spread due to a lack of effective vaccines and pre-exposure prophylaxis methods, even though the availability and effectiveness of antiretroviral therapy has helped reduce acquired immunodeficiency syndrome (AIDS)-related deaths.
The technology is directed to compositions and methods of designing nucleic acid nanoparticles (NANPs) composed entirely of DNA, RNA, or DNA and RNA to achieve desirable immunostimulation and decrease undesirable effects on the immune system by changing the composition of the NANP. Benefits of the invention include the desirable activation of the immune system by these particles to increase the efficacy of vaccines and immunotherapies.
The degradation of archival surgical and biospecimen limits the utility of many biomarkers that may have prognostic or predictive significance in guiding a patient’s therapy. Previous methods at preventing the degradation of RNA and proteins in formalin fixed, paraffin embedded (FFPE) tissue blocks & slides have no protective benefit.
Adoptive cell therapy (ACT) is an attractive new therapeutic approach for treating various cancers. ACT has recently demonstrated a high degree of efficacy when treating patients with hematological malignancies. However, to date, no effective Chimeric Antigen Receptors (CAR) T cell therapy exists for solid tumors.
Chimeric antigen receptors (CARs) combine an antibody-based binding domain (and single chain fragment variable region, scFv) with T cell receptor signaling domains (CD3 zeta with a costimulatory domain, typically CD28 or 41BB). When T cells express CARs, they are activated in a major histocompatibility complex- (MHC) independent manner to kill tumor cells expressing the target to which the scFv binds. CAR T cells targeting the B cell antigen CD19 have resulted in remissions in 60-80% of patients with pre-B cell precursor acute lymphoblastic leukemia (BCP-ALL).