Leptin—A Strong Helper to Vaccinia Virus in Tumor Treatment
Vaccinia virus is the first virus that has been shown to be efficient and safe in tumor treatment, and its combination with leptin is proved to have stronger effect.
Vaccinia virus is the first virus that has been shown to be efficient and safe in tumor treatment, and recent study has proved that the combination between vaccinia virus and leptin will show stronger effect.
Vaccinia virus, a kind of DNA virus showing an oval brick shape, belongs to Poxvirus. As a vaccine against smallpox infections, it has been used for more than 200 years and has detailed data to prove its safety for human, making it a very attractive platform for oncolytic treatment. In addition, the virus can accommodate and express therapeutic transgenes over 50 kb and has a variety of known mechanisms of action against human and rodent tumors. Vaccinia virus (VV) is the first virus that has been shown to form a consistent and persuasive infection in the tumor bed after intravenous injection.
However, there are still many challenges in the widespread commercialization of oncolytic vaccinia viruses. Like other oncolytic virus platforms, patients need to be given large doses of viral products. To achieve this dose, viruses are often produced and used in adherent tumor cell culture with serum-containing medium. In order to meet the regulations, a large number of virus products need to be tested to ensure that there is no carcinogenic DNA in the final product.
Another challenge in the production of pharmaceutical grade vaccinia virus is its relatively large particle size, so it cannot pass through a sterilization filter with a pore size of 0.2 μm or less. This means that the entire production process needs to be carried out under sterile conditions. Vaccinia virus is very stable when stored at -80°C, but additional formulation studies are required to obtain pharmaceutical grade products that can be stored at -20°C, 4°C, or even room temperature.
Recently, Cell’s sub-imprint Immunity published the latest research results of the Stephen H. Thorne research team of the University of Pittsburgh titled Oncolytic Viruses Engineered to Enforce Leptin Expression Reprogram Tumor-Infiltrating T Cell Metabolism and Promote Tumor Clearance. It innovatively used non-immune-related genes to construct new oncolytic viruses and achieved good therapeutic effects.
Leptin (LP) is a protein hormone secreted by adipose tissue, mainly produced by white adipose tissue. It was generally believed that after entering the blood circulation, it will participate in the regulation of sugar, fat and energy metabolism, prompting the body to reduce food intake, increase energy release, inhibit the synthesis of fat cells, and thus reduce weight. The function of leptin is multi-faceted, mainly manifested in the regulation of fat and body weight.
Some research data show that leptin protein can enhance the metabolic function of T cells in vivo and in vitro. Therefore, the researchers conducted experiments using melanoma cells (CL24) and pancreatic cancer cells (Panc02) to establish animal tumor models, and constructed an oncolytic vaccinia virus that overexpressed leptin (VVleptin), comparing with VV group and PBS control group. The results show that both VV and VVleptin can effectively inhibit the growth of tumors, and VVleptin has the best effect, which achieves the infiltration of effector T cells into the tumor tissue and the reconstruction of the tumor microenvironment, and thus can significantly prolong the survival period. In addition, the data show that the immune stimulation effect of VVleptin is better, and after VVleptin treatment, mice have acquired immune memory, which can resist the reinfection of tumor cells of the same kind.
Oncolytic virus is an important direction of tumor immunotherapy with huge market potential, and may become another major breakthrough after immune checkpoint inhibitor drugs. With an experienced expert team, Creative Biolabs provides customized, standardized, reliable and high-quality oncolytic virus therapy development services for clients globally, covering all aspects from virus engineering, cell biology to animal testing with a special emphasis on virus engineering and in vitro and in vivo validation.
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