Neuroblastoma is a rare pediatric cancer that affects one in every hundred thousand children under the age of fifteen in the United States. Current standards of care  are chemotherapy and surgery, followed by stem-cell treatments, radiation and anti-ganglioside antibody therapy, which yield an average three-year survival rate of 10-45%. This demonstrates a need for more effective therapies.

Immortalization of plasma cells leads to plasma cell malignancy diseases such as multiple myeloma (MM). B-cell maturation antigen (BCMA) is a protein that is preferentially expressed by malignant and normal B cells and plasma cells, butnot on other cells in the body. This limited expression profile suggests that BCMA is a promising target for anticancer therapeutics for cancers in which there is excess production of plasma cells and B cells. 

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.

Neuroblastoma is a rare pediatric cancer with approximately 1,000 new cases arising annually. Current therapies have a less than forty-five percent (45%), three-year survival rate which demonstrate a need for a more effective treatment against this disease. Glypican-2 (GPC2) is a cell surface protein that is preferentially expressed in pediatric cancers including neuroblastoma, which makes GPC2 an attractive candidate for targeted therapy. 
 

Human papillomavirus (HPV) has been linked to many cancers including cervix, uterine, anus, vulva, vagina, and penis. Although HPV vaccines exist to prevent HPV-associated cancers, there are still more than 5,000 deaths caused by HPV-associated cancers each year in the US and cervical cancer continues to be the second leading cause of cancer death in women ages 20 to 39.

The thymus is an integral part of the adaptive immune system as it generates T cells. Its function diminishes rapidly as the body ages, leading to a compromise of the immune system in the elderly. Reconstitution of adaptive immunity through mass production of different T cell types is therefore a therapeutic need in immunocompromised populations. Furthermore, production of T cells with specific receptors targeting cancer cells is an important cancer immunotherapy approach.

Tuberculosis (TB) is an infectious disease that typically affects the lungs. Current therapies include a panel of antibiotics given over a range of 6-9 months. As a result of the expense of treatment, the extended timeframe needed for effective treatment, and the scarcity of medicines in some developing countries, patient compliance with TB treatment is very low and results in multi-drug resistant TB (MDR-TB). There remains a need for a faster, more effective treatment for TB.