Why IL-2 and cytokines are important in cancer

The term “cytokine” is derived from a combination of two Greek words – “cyto” meaning cell and “kinos” meaning movement. Cytokines are cell signaling molecules that aid cell to cell communication in immune responses. They are any number of small proteins secreted by various cell types. These molecules carry signals locally and systemically to a variety of cells. They are responsible for up-regulating (turning on), as well as down-regulating (turning off) the immune response. The immune system is also important in preventing and fighting cancer. Cancer can survive by blocking your immune system’s ability to detect and fight cancer.

Cancer patients often have a weakened immune system. One way that cancer weakens the immune system is by turning off the certain immune cells so that they are no longer able to fight the cancer. This may allow for the tumor to continue growing. If the tumor is removed, a weakened immune system may allow the cancer to come back.

Interleukin-2 (IL-2) is a type of cytokine. One of a group of related proteins made by leukocytes (white blood cells) and other cells in the body. IL-2 is made by a type of T lymphocyte. It increases the growth and activity of other T lymphocytes and B lymphocytes and affects the development of the immune system. The potential of IL-2 in stimulating the immune system to help fight cancer has been understood for some time however it’s clinical application has been limited by toxicities associated with the recombinant versions of IL-2.

The high-dose rIL-2 toxicity is largely caused by 2 mechanisms. One is the rapid and the overactive stimulation of the immune system leading to chemical reactions that can cause vasodilation and hypotension associated with less perfusion of blood into the organs. This can lead to organ dysfunctions in the kidneys, the heart, and the liver. IRX-2 provides IL-2 and other cytokines in physiologic doses. It is speculated that toxicities previously attributed to cytokines may potentially be associated with high doses administered.

The second aspect of the toxicity is related to the alpha subunit of the IL-2 receptor, which is also expressed on endothelial cells, in particular in the pulmonary lung endothelial cells. Activation of the alpha subunit by IL-2, can lead to leaky vascular syndrome, which is associated with pulmonary edema, which has become a big hurdle for IL-2 and limits which patients can be treated with recombinant forms of IL-2. This is also speculated to be dose related, and it may be postulated that the physiologic doses of cytokines in IRX-2 may not be associated with this adverse event.

Brooklyn ImmunoTherapeutics is developing IRX-2, which delivers human blood cell-derived IL-2 and other key cytokines, a unique formulation, at physiologic levels, specifically designed to potentially restore immune function in the tumor microenvironment, enabling the immune system to attack cancer cells.

In Vivo Gene Editing