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Hematopoietic and pluripotent stem cells can be differentiated into T cells with potential clinical utility. Current approaches for in vitro T cell production rely on Notch signaling and artificial mimicry of thymic selection. However, these approaches result in unconventional or phenotypically aberrant T cells; which may lead to unpredictable behavior in clinical use. Thus, there exists a need for improved methods of generating conventional T cells in vitro from stem cells.
 

RNA interference (RNAi) is a biological response to double-stranded RNA that regulates expression of protein-coding genes and is a natural mechanism for gene silencing. Delivery of short, interfering RNA (siRNA) leads to RNAi of the targeted genes. 

Bladder cancer is the fifth most common cancer in the United States and one of the costliest cancers to treat. Compared to other cancer types, bladder cancer has been understudied, and there is a need for informative mouse bladder cancer models that resemble the clinical situation and allow for evaluation of chemotherapeutic or immunotherapeutic agents. The orthotopic murine bladder cancer model MB49 resembles non-muscle invasive, nonmetastatic urothelial carcinomas and provides an opportunity to study the anti-tumor effects of immune cell checkpoint inhibitors.

Peptides corresponding to transmembrane domains of a number of integral proteins were discovered to spontaneously self-assemble in aqueous solutions into stable and remarkably uniform nanoparticles.  Researchers at the NCI’s Cancer and Inflammation Program have developed fully synthetic, peptide-based, virus-like nanoparticles capable of delivering cytotoxic, radioactive, and imaging agents. 

Structure and function of tumor-target self-assembling particles:

Adoptive cell therapy (ACT) using tumor-specific T cells can produce positive clinical responses in some cancer patients. Nevertheless, several obstacles to the successful use of ACT for the treatment of cancer and other conditions remain. For example, one or more of the in vivo persistence, survival, and antitumor activity of tumor-specific T cells can, in some cases, decrease following adoptive transfer. Accordingly, there is a need for methods of obtaining a robust population of tumor-specific T cells for ACT.

Immune checkpoint inhibitors (e.g. CTLA-4, PD-L1) have recently shown significant promise in the treatment of cancer.  However, when used alone, these checkpoint inhibitors are limited by the absence or repression of immune cells within the targeted cancer.  For those cancers associated with these limited immune systems, there remains a need for effective therapies.  Agents capable of recruiting and activating immune cells to these types of cancers could extend the overall and complete response rates of combination therapies within the immunooncology domain. 

The baculovirus-based protein expression system has gained increased prominence as a method for expressing recombinant proteins that are used in a wide range of biomedical applications. An important step in the use of this system is the ability to determine the virus infectious titer, i.e., the number of active baculovirus particles produced during an infection of the insect host cell.

Cancer is the second leading cause of death worldwide. The primary cause of mortality from cancer is metastasis. While the underlying mechanisms of cancer metastasis are still being unraveled, the gp78 protein involved in ER-associated degradation (ERAD) appears to play a role in metastasis in sarcoma. Targeting gp78 may be a therapeutic option in cancer treatment.

Interleukin-15 (IL-15) and IL-21 have been reported to support the function of anti-tumor T cells.  However, their use in the clinic has been constrained, in part, by dose-limiting toxicity and the need for repeated administration.  To overcome these limitations, researchers in the National Cancer Institute (NCI) Experimental Transplantation and Immunology Branch (ETIB) have developed synthetic IL-15 and IL-21 molecules for autocrine expression by the engineered therapeutic T cel

Primary liver tumors and secondary hepatic malignancies are among the leading causes of cancer-related deaths. Liver metastases account for 95% of all hepatic cancers, and the liver is the most common site for organ metastasis in the body. The gut microbiome serves an important role in antitumor immunity regulating the efficacy of chemo- and immunotherapies. The liver is exposed to gut bacteria through blood from the intestine, with 70% of the whole liver’s blood supply coming from intestinal blood. Changes in the commensal microbiome may affect immune cell function in the liver.