Adoptive T-cell therapy (ACT) utilizes tumor-reactive T cells to induce disease remission. While ACT has been used effectively to treat metastatic melanoma and certain epithelial cancers, most patients do not respond to treatment. Although the mechanisms underlying this variable response to therapy are not fully elucidated, the phenotype of the adoptively transferred cell is known to be a key determinant of treatment efficacy.

Researchers at the National Cancer Institute (NCI) have developed a method of stimulating an immune response in humans at risk for infection by, or already infected with, an Human Immunodeficiency Virus (HIV)-1 retrovirus. This method utilizes deoxyribonucleic acid (DNA) vaccines to stimulate CD8+ T cell immune responses. The DNA vaccine encodes antigens known to be effective against retroviruses, such as HIV-1gag, gp120, nefCTL, and proCTL. The same antigens are also expressed by the pox virus vaccine, which elicits an increased immune response when combined with the DNA vaccine.

Mantle cell lymphoma (MCL) is a group of aggressive B-cell lymphomas displaying heterogeneous outcomes after treatment.  Some patients have the slowly progressing disease that does not require immediate treatment, while others have a disease that rapidly progresses despite highly aggressive treatment. A number of prognostic tools have been described to determine whether patients have slow or rapidly progressing diseases, including the mantle cell lymphoma International Prognostic Index (MIPI) and biomarkers, such as KI-67.

The National Cancer Institute is seeking parties interested in collaborative research to co-develop, evaluate, or commercialize a new mouse model for monoclonal antibodies and immunoconjugates that target malignant mesotheliomas.  Applications of the technology include models for screening compounds as potential therapeutics for mesothelioma and for studying the pathology of mesothelioma.

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.

Chk2 is a protein kinase activated in response to DNA double strand breaks. In normal tissues, Chk2 phosphorylates and thereby activates substrates that induce programmed cell death, or apoptosis, via interactions with p53, E2F1, PML proteins. In cancer tissues, where apoptosis is suppressed, Chk2 phosphorylates and inactivates cell cycle checkpoints (via interactions with Cdc25, phosphatases and Brca1 proteins), which allows cancer cells to repair and tolerate DNA damage.

The development of RNA-based nanostructures and their use in a variety of applications, including RNA interference (RNAi) and drug delivery, represents an emerging field of science, technology, and biomedicine.  RNA is a dynamic material because of its natural functionalities, its ability to fold into complex small structures, and its capacity to self-assemble. 

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

Tumors can develop unique genetic mutations which are specific to an individual patient. Some of these mutations are immunogenic; giving rise to autologous T cells which are tumor-reactive. Once isolated and sequenced, these neoantigen-specific TCRs can form the basis of effective adoptive cell therapy cancer treatment regimens; however, current methods of isolation are inefficient. Moreover, the process is technically challenging due to TCR sequence diversity and the need to correctly pair the a and b chain of each receptor.

Cervical cancer is one of the most common cancers among women worldwide. Currently, physical descriptors such as tumor size and depth are the primary factors used for deciding the course of treatment. Despite significant efforts to identify prognostic biochemical markers or therapeutic targets to improve diagnosis and treatment, none have achieved routine clinical use. An example of one previously identified biomarker is the Tn antigen, a carbohydrate moiety composed of a GalNAc residue linked to serine or threonine.