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Advanced stage cancers are typically marked by metastases of the primary cancer to secondary sites such as lungs, liver, and bones. Such metastatic cancers result in strikingly low 5-year survival rates, underscoring the need for novel therapeutics. For example, bone metastasis of primary breast cancer has a 5-year survival rate of 13%, lung cancer only 1%. There is a need for targeted therapy options specific to metastases. One approach to targeting metastases is to reduce cancer cell migration and invasion.

Most early work on CD133 was carried out using one of two monoclonal antibodies (mAbs), AC133 and AC141, which recognize an undefined glycosylated epitope of CD 133.

There are no analgesics to ameliorate chronic pain without adverse side-effects (e.g., respiratory depression, gastrointestinal effects, tolerance, dependence), thus forcing patients into a difficult choice of negative impacts on quality of life. Most of the analgesics used for chronic and acute pain are drugs such as oxycodone, morphine, oxymorphone, and codeine. All of these opioids have been subject to misuse; prescription drug abuse is a severe problem worldwide, causing high mortality and greatly increased emergency room visits.

Cancer cells can upregulate autophagy – cell destruction – as a response to chemotherapy. Investigators in Dr. Melvin DePamphilis’ laboratory at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have shown that compounds identified by screening a library of compounds blocks autophagy in some cancer cells (e.g., melanoma) but are not toxic to normal cells. Cancer cells with mutations in the BRAF oncogene are especially dependent on autophagy. Treatment of cancer cells with the BRAF mutation can increase the efficacy of chemotherapy.

HCC is the most frequent malignant tumor in the liver and the third leading cause of cancer death worldwide.  A progressive sequence of somatic mutations and epigenetic changes of oncogenes or tumor suppressor genes are believed to cause tumor development. However, high genomic instability in tumors causes the accumulation of genomic aberrations that do not contribute to tumor progression. Therefore, it is important to distinguish between ''driver'' mutations that are functionally important and ''passenger'' mutations that do not provide a selective advantage to the tumor cells.

Exposure to ionizing radiation or agents that induce DNA double-stranded breaks (DSBs), which is one of the most damaging types of lesions in DNA, can result in damage to cells and/or tissues.  Thiscan lead to illness (i.e., Acute Radiation Syndrome, Cancer) or death.  Identifying the amount of exposure to a DNA DSB-causing agent can be useful in determining the need for further testing, avoidance or modification of certain medical procedures, and/or types of medical treatments.

One problem with the development of immunotherapy for cancer or other diseases is the inability to stimulate a sufficient immune response in patients to tumor associated antigens. The Linker Adapted for T Cell Signaling molecule (LAT) has been shown to be an important molecule in T cell signaling. The inventions described and claimed in this patent application illustrate a new supportive role for LAT which may be harnessed to improve a patient's immune response to tumor-associated antigens.

Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody binding fragment fused to protein signaling domains that cause T-cells which express the CAR to become cytotoxic.  Once activated, these cytotoxic T-cells can selectively eliminate the cells which they recognize via the antibody binding fragment of the CAR.  Thus, by engineering a T-cell to express a CAR that is specific for a certain cell surface protein, it is possible to selectively target those cells for destruction.  This promising new therapeutic approach is known as adoptive cell therapy.

Research and development leading to the discovery of novel antibiotics has waned in recent years. At the same time, the emergence and spread of antimicrobial resistance has compounded the global danger to human health from bacterial infections. 

Adoptive Cell Therapy (ACT) is a promising technique that uses a patient's own T cells to treat cancer. The process requires removing and engineering a patient's T cells to express a chimeric antigen receptor (CAR) or T cell receptor (TCR) that targets a specific cancer antigen. When the modified T cells are reintroduced into the patient, the T cells attack and kill cancer cells that express the antigen, thereby treating the patient.