Researchers at the NCI Laboratory of Molecular Theranostics and the Molecular Imaging Program have developed a new method to modify, isolate and remove a single chemically-labeled molecule or a cluster of proteins associated with the chemically-labeled protein. The chemical label can be an antigen-antibody complex. This discovery is based on the mechanism of photo-immunotherapy (PIT).
Current methods of labeling and synthesizing RNA do not allow for multiple labels or long RNA segments to be synthesized for large RNA on a milligram scale.
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.
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
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.
Hyperthermia has been used extensively and successfully in the treatment of solid tumors. For accessible solid tumors with impressive efficacy not amenable to surgery, ablative hyperthermia (>55°C for 20 s to 15 min) has been used as a definitive treatment. By contrast, for both radiotherapy and chemotherapy, mild hyperthermia (40-45°C for up to 1 hour) has been shown useful as an adjuvant.
Adoptive cell therapy (ACT) uses cancer reactive T-cells to effectively treat patients. However, several obstacles inhibit the successful use of ACT for cancer treatment. Current approaches for the expansion of T-cells may produce T-cells with a terminally differentiated phenotype that is associated with diminished anti-tumor activity and poor capacity for long-term persistence. Thus, there is a need for improved methods of obtaining an isolated population of effective T-cells for ACT.