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 (IL)-34 is a homodimer that is produced mainly by keratinocytes, neuronal cells and regulatory T cells (Tregs). It is believed to play important roles in chronic inflammation and the homeostasis of microglia. Currently, there is no effective treatment for many types of retinal degeneration. An improved treatment of autoimmune uveitis is also needed, as current uveitis treatment primarily uses steroidal anti-inflammation medication, which may produce significant unwanted side effects in long-term use.
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.
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.
Substance use disorder is a chronic medical condition, taking its toll on our public health care and judicial systems in an economically unsustainable way. More than 20 million Americans suffer from substance use disorders.
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.
Proinflammatory T-helper 17 cells (Th17) play important roles in host immune defense against infection, but uncontrolled activation of these cells, known as the Th17 response, may cause autoimmune and autoinflammatory diseases (uveitis, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease) through the effects of Th17 lineage cytokines (such as, IL-17F, IL-22 and GM-CSF). Importantly, IL-17A (a proinflammatory cytokine) represses other Th17 lineage cytokines by upregulating the regulatory cytokine IL-24.
The accurate placement of transplanted tissue at a precise position in the retina is difficult but critical for a successful implementation of an ocular surgical intervention.
Gammaretroviral vectors were the first viral gene-therapy vectors to enter clinical trials and remain in use. One potential hazard associated with the use of such vectors is the presence of replication-competent retroviruses (RCR) in the vector preparations – either as a result of: 1) recombination events between the plasmids used for vector production, 2) interactions between the plasmids and endogenous retroviral sequences in the packaging cell lines, or 3) as a result of contamination in the laboratory.