Poliovirus therapy activates immune response against cancer

An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that prevent cancer cells to evade the immune system.

Glioblastoma is a lethal form of brain cancer. The research team elucidated how the poliovirus works not only to attack cancer cells directly, but also activates longer-lasting immune response that appears to inhibit regrowth of the tumor.

Using human melanoma and breast cancer cell lines, and then validating the findings in mouse models, the researchers found that the modified poliovirus therapy starts by attaching to malignant cells, which have an abundance of CD155 protein.

The CD155 protein is a poliovirus receptor. The modified virus then begins to attack the tumor cells, directly killing many, but not all. This releases tumor antigens. The second phase of assault is more complicated, by killing the cancer cells, the modified poliovirus triggers an alarm within the immune system, alerting the body's defenses to attack.

This appears to occur when the modified poliovirus infects dendritic cells and macrophages. Dendritic cells then present tumor to T cells to launch an immune response. Once the immune system is activated against the poliovirus-infected tumor, the cancer cells can no longer hide and they remain vulnerable to ongoing immune attack.

Poliovirus killed tumor cells and infected the antigen-presenting cells, which allows them to function in such a way that they can raise a T-cell response that can recognize and infiltrate a tumor. Poliovirus stimulates an innate inflammatory response.
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Targeted cell metabolism can improve immune system

Immune system can become so over-activated when fighting infections that the resulting inflammatory response can lead to death. Excessive response by the immune system can be modulated by targeted manipulation of the sugar metabolism to produce an immune response that eliminates the pathogens without causing any harmful to the immune system.

Using 2-Deoxy-D-glucose 2-DG during the infection make this possible, adding 2-DG, that prevents glycolysis, causes increased production of interleukin-12 IL-12, a pro-inflammatory cytokine, while suppressing the production of interleukin-10, an anti-inflammatory cytokine.

IL-12 triggers a specific T-cell immune response, which is part of the cellular immune response, to specifically boost the defence mechanisms that serve to eliminate intracellular pathogens like listeria. Addition of 2-DG changes the nature of the immune response and the intensity of the inflammatory process, inflammation is controlled so that the immune system is able to manage the situation without allowing the infection to leads to a deadly outcome.

This prevents excessive inflammatory responses, following addition of of 2-DG, only p40 is upregulated, while no p35 is produced. This modified cytokine profile, there is also a simultaneous increase in IL-23 expression which could subsequently bring about modified recruitment of immune cells and hence have a decisive influence on the intensity of the immune response.

The metabolic increased production of activating mediators with simultaneous inhibition of immunosuppressive mediators. Manipulation of the sugar metabolism and associated modulation of the immune system could open up new options for treating specific infectious and autoimmune diseases
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How HIV affects the immune system

Human Immunodeficiency virus (HIV) is a lentivirus that causes HIV and later AIDS. Early signs of HIV are: fever, joint pain, sore throat and skin rashes.

A T-cell is a type of lymphocyte - white blood cell that defend the body against disease, HIV infects a cell by attaching itself to T-cell, multiplies its virus and destroy the T-cell.

CD4 count shows the strength of one's immune system which is between 500 1500 for healthy people, being infected with HIV without treatment will reduce the count below 200.

 HIV  exposes the infected person to opportunistic  infections like: pneumonia, toxoplasmosis, thrush, and tuberculosis.

Presently, there is no cure for HIV. Antiretroviral therapy is recommended for people living with HIV virus.

Common side effects of Antiretroviral drugs are: glucose intolerance, kidney failure, hepatitis of the liver, insulin resistance, osteoporosis, anemia and inflamed pancreas.