Combined RNA and DNA Vaccination Strategy for Improving the Vaccine Immune Response

The development of an effective HIV vaccine has been ongoing. HIV sequence diversity and immunodominance are major obstacles in the design of an effective vaccine. Researchers at the National Cancer Institute (NCI) developed a novel vaccine strategy combining both DNA and mRNA vaccination to induce an effective immune response. This combination strategy could also be used to develop vaccines against cancer or other infectious diseases (ex. SARS-CoV-2). 

Methods of Predicting Patient Treatment Response and Resistance via Single-Cell Transcriptomics of Their Tumors

Tailoring the best treatments to cancer patients remains a highly important endeavor in the oncology field. However, personalized treatment courses are challenging to determine, and technologies or methods that can successfully be employed for precision oncology are lacking.

National Cancer Institute Dosimetry System for Nuclear Medicine (NCINM) Computer Program

Nuclear medicine is the second largest source of medical radiation exposure to the general population after computed tomography imaging. Imaging modalities utilizing nuclear medicine produce a more detailed view of internal structure and function and are most commonly used to diagnose diseases such as heart disease, Alzheimer’s and brain disorders. They are used to visualize tumors, abscesses due to infection or abnormalities in abdominal organs.

Novel Human Islet Amyloid Polypeptides as Alzheimer’s Disease Biomarkers and Inhibitors of Amyloid Formation

Over 34 million Americans are living with diabetes. An estimated 6.5 million Americans are living with Alzheimer’s disease (AD) and type 2 diabetes mellites (T2DM). Amyloidosis due to aggregation of amyloid-β is key pathogenic event in AD, whereas aggregation of mature islet amyloid polypeptide (IAPP37) in human islet leads to β-cell dysfunction. A hallmark feature of T2DM is the accumulation of islet amyloid polypeptide fibrils in pancreatic islets. Such accumulations form amyloid plaques and cause apoptosis of -cells of islets. 

National Cancer Institute dosimetry system for Computed Tomography (NCICT) Computer Program

About half of the per capita dose of radiation due to medical exposures is provided by computed tomography (CT) examinations. Approximately 80 million CTs are performed annually in the United States. CT scans most commonly look for internal bleeding or clots, abscesses due to infection, tumors and internal structures. Although CT provides great patient benefit, concerns exist about potential associated risks from radiation doses – especially in pediatric patients more sensitive to radiation.

T Cell Receptor Targeting CD22 for the Treatment of Lymphomas and Leukemias

CD22 is a protein expressed by normal B cells and B-lymphoid malignancies. Its limited tissue expression pattern makes it a safe antigen for targeted therapies, such as T-cell Receptor (TCR)-T cell therapy. CD22-targeting therapies already on the market, mainly antibody-immunotoxin conjugates and chimeric antigen receptors (CAR)-T cells, have limitations such as resistance to treatment and/or side effects. Resistance mechanisms to the current CD22 therapies involve loss or modulation of target antigen on the cell surface.

T Cell Receptors Targeting CDKN2A Mutations for Cancer Immunotherapy

Cyclin-dependent kinase inhibitor 2A gene, also known as CDKN2A, is a tumor suppressor gene and is commonly inactivated through somatic mutations in many human cancers. For example, inactivation of CDKN2A is highly prevalent in melanoma, gastrointestinal and pancreatic cancers. Through germline mutations, CDKN2A is associated with predisposition for a variety of cancers, including melanoma and pancreatic cancers. Despite the high frequency of CDKN2A mutations in cancer, there have been no successful therapies targeting these mutations to date.

Novel Small Molecule Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) for Treatment of Solid Tumors

Topoisomerase 1 (TOP1) is an essential enzyme that plays a critical role in DNA transcription and replication. TOP1 inhibitors are a known class of anti-cancer agents that work to interrupt DNA replication in cancer cells, causing cell death. Since the discovery of the TOP1 inhibitor camptothecin (CPT) from plant extracts more than 60 years ago, two CPT analogs (irinotecan and topotecan) were approved by the FDA for cancer treatment. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme involved in DNA repair created when TOP1 is inhibited.

Cell Lines that Constitutively Express High-Frequency KRAS and P53 Mutations and Human Leukocyte Antigens (HLAs)

Adoptive cell therapy (ACT) is a breakthrough form of cancer immunotherapy that utilizes tumor infiltrating lymphocytes (TILs) or genetically engineered T cells to attack tumor cells through recognition of tumor-specific antigens. A major hurdle in the development of ACT is the identification and isolation of T cells that recognize antigens that are expressed by tumor cells but not by healthy tissues. Current methods to identify such T cells involve extracting autologous antigen presenting cells (APCs) from patients in an expensive, laborious, and time-consuming process.