Gene therapy is a promising strategy to treat a wide range of human diseases, and several gene therapy vectors have been developed to deliver these novel treatments. However,  risks and challenges of using these vectors remain, such as: gene integration, potential infection, immune response and maintaining long term, stable gene expression. Human artificial chromosomes (HACs) provide a unique opportunity to develop a new generation of nonviral vectors for therapeutic use as gene expression and delivery systems.

Researchers at NIH/NICHD have identified approximately 200 proteins as candidate molecules (leads) that “fine tune” T cell receptor (TCR) signaling. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) seeks partners to collaborate on in vitro studies to validate these potential immunomodulators and to conduct in vivo studies in a murine cancer model to determine the effects of ligands (e.g. antibodies) to the proteins to determine their effect on the immune response to cancer cells.

Thymoma and thymic carcinomas are a rare and poorly understood group of malignancies.   Despite the growing number of biomarkers that are used for diagnosing and treating carcinomas in general, cancers of the thymus are still diagnosed, stratified and treated by a costly combination of histology, surgery and radiological procedures.  The lack of qualified biomarkers associated with thymomas and thymic carcinomas has also hampered the development of targeted therapies.

Hepatocellular Carcinoma (HCC) is one of the most common cancers worldwide with largely unfavorable outcomes due to a lack of effective treatment options for patients in the later state of disease. The gold standard of care for HCC patients with intermediate to locally advanced tumors is transcatheter arterial chemoembolization (TACE), a procedure whereby the tumor is targeted both with local chemotherapy and restriction of local blood supply. TACE procedures are often not effective however, and a need exists to identify patients that will respond to TACE.

Problem: Cryopreservation is a process where living biological materials like cells, tissues, and cell therapies (which are susceptible to damage caused by unregulated chemical kinetics) are preserved by cooling to very low temperatures in the presence of specific cryopreservation media that protects the biological material from damage. In order to be used, the biological material ideally should be thawed in a controlled manner that minimizes damage and desirably brings the material back to a viable state.

Mesothelioma is an aggressive cancer covering anatomic surfaces (e.g. lining of the lungs, heart, abdomen, etc.) that resists multi-modality therapies. Regional recurrence of mesothelioma from residual tumor cells prevents long-term benefits after surgical resection. Furthermore, there is no clinical consensus on intracavitary adjuvants that are effective in extending the tumor reduction effect of surgery.

DNA or RNA-based diagnostic tests for infectious diseases are critical in modern medicine. The current gold standard for COVID-19 detection is testing SARS-CoV-2 viral RNA by quantitative reverse transcription Polymerase Chain Reaction (RT-qPCR). This method involves patient sample collection with a nasopharyngeal swab, storage of the swab in a universal transport medium during transport to testing site, RNA extraction, and analysis of the extracted RNA sample.

T cells with T cell receptors (TCRs) for cancer-specific antigens are used for adoptive cell therapy (ACT), wherein a patient’s T cells are redirected against their own cancer. However, these isolated T cells may require further ex vivo manipulation to enhance their anti-tumor activity. The ex vivo manipulation of these T cells, or the selection of less functionally inert T cells, and genetic insertion of tumor specific TCRs may circumvent these limitations.

The  National Cancer Institute (NCI) is seeking parties interested in licensing software for the automated determination of macromolecular structures using cryo-electron microscopy.

T cell-based immunotherapy (such as CAR therapies) is a promising approach for the treatment of several cancers. However, T cells currently employed for various T cell-based immunotherapies are usually senescent and terminally differentiated leading to poor proliferative and survival capacity, limiting their therapeutic effectiveness once transferred into a patient’s blood.