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Medical imaging is an important resource for early diagnostic, detection, and effective treatment of cancers. However, the screening and review processes for radiologists have been shown to overlook a certain percentage of potentially cancerous image features. Such review errors may result in misdiagnosis and failure to identify tumors. These errors result from human fallibility, fatigue, and from the complexity of visual search required.

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 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.

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).

Researchers at the National Cancer Institute (NCI) have developed a method of stimulating an immune response in humans at risk for infection by, or already infected with, an Human Immunodeficiency Virus (HIV)-1 retrovirus. This method utilizes deoxyribonucleic acid (DNA) vaccines to stimulate CD8+ T cell immune responses. The DNA vaccine encodes antigens known to be effective against retroviruses, such as HIV-1gag, gp120, nefCTL, and proCTL. The same antigens are also expressed by the pox virus vaccine, which elicits an increased immune response when combined with the DNA vaccine.

Researchers at the National Cancer Institute (NCI) have developed a new method of improving the efficacy of vaccines in patients with human immunodeficiency virus (HIV) by activating Ras. This method can be used to develop more efficacious vaccine compositions by activating Ras before, during, or after vaccination. Additionally, the researchers discovered that modulation of the Ras pathways could be a predictive biomarker of protection against HIV.