Drugs targeted against Fractalkine signaling poised to offer major breakthrough in the treatment of autoimmune diseases and cancer

Non-specific immune system becomes increasing area of focus

Fractalkine signaling is increasingly attracting interest as a potentially major drug target. Several recent exploratory clinical studies have showed  desired effects against intractable forms of autoimmune diseases in humans, including  the use of an antibody E6011 to block Fractalkine by Eisai Pharmaceuticals. These results support the strong effects of Fractalkine blocking that have already been shown in research studies by Kancera with their lead molecule KAND567. The company believes that together, these results show that a blockade of Fractalkine signaling could form the basis of a significant new class of medicines for diseases caused or aggravated by the human immune system, including autoimmune diseases and cancer. 

The majority of the currently available autoimmune drugs block either the entire immune system or target the specific immune system. These drugs have been successful, but for a significant proportion of patients they are not effective enough. In addition, these drugs can cause an increased risk of infection, as well as very serious side effects and even cancer.

For these reasons several groups of researchers have switched their focus to developing drugs that selectively target  the  non-specific immune system, which quickly, and without requiring training, can attack against foreign bodies. The non-specific immune system has also been linked to several serious diseases, mediated by immune cells called macrophages. These diseases include cancer and inflammation of the stomach, joints, nerves and blood vessels .

The Eisai and Kancera drug candidates directed against the Fractalkine system represent two sides of the same coin, i.e. they operate at different ends of the Fractalkine system (signal transmitter and receiver). Both E6011 and KAND567 are expected to act in the bloodstream to prevent immune cells from penetrating the tissue, and causing or maintaining inflammation. KAND567 is expected to have an advantage over an antibody since it is a small molecule that can be administered orally and more easily penetrate tissues outside the blood vessels to exert its effect.

The Esaii clinical studies showed that blockade of Fractalkine signaling significantly reduces the severity of Crohn's disease and rheumatoid arthritis and, in some cases, the treatment results in remission. These effects have been demonstrated in patients who do not respond to or tolerate the current best medicines for autoimmune diseases (anti-TNF therapy). The studies were performed using an injectable antibody against Fractalkine (E6011) that was developed by the Japanese CAN Research Institute and then tested by Eisai.

Kancera’s initial preclinical results in a disease model for multiple sclerosis supported the idea that treatment with KAND567 produces the desired effect against autoimmune disease without significant side effects on the specific immune system. However, more recent studies have also shown that KAND567 can have a role in cancer by reducing the nerve damage associated with chemotherapy. Since there is currently no effective treatment for this neuropathy, this breakthrough could pave the way for more effective treatment treatment regimes by counteracting dose-limiting side effects.

These results have also led Kancera to start investigating whether Fractalkine-blocking drugs can directly attack cancer cells. Several types of cancer cells have namely acquired capabilities from the non-specific immune system. One of the abilities that cancer cells have "hijacked" is to use the Fractalkine system to spread within the body, just as the immune system does. If KAND567 can block this capability of cancer cells, there is potential for preventing or reducing metastasis.

Based on all of the above, Kancera AB has decided to implement a Phase I clinical study of KAND567  to document the drug substance’s properties and safety in humans. 

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