Scientific concept

An antibody with a large number of possibilities

Cantargia is developing an antibody-based cancer treatment, CAN04, that attacks the cancer in two different ways. CAN04 stimulates the body's natural killer cells to recognize and kill the tumour cells directly, while also blocking the inflammatory pathways that tumours use to create a ‘fertile soil’ in which to proliferate and expand.

How CAN04 attacks a cancer tumour. Watch the animated video.


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The tumour’s microenvironment

Cancer is a common name for over 200 different diseases that all are associated with genetic changes in cells, causing them to proliferate out of control. Traditional cancer treatments are designed to target rapidly proliferating cells, but these products rarely provide a cure of the disease. Furthermore, this type of treatment can cause serious side effects because it also affects other healthy cells that divide quickly in the body (e.g. in the intestine, hair follicles, oral mucosa).

Tumours are made up of several different cell types besides the cancer cells themselves [1]. They also comprise the blood vessels that provide nutrition, “stromal cells”, serving as a skeleton, and inflammatory immune cells. Inflammation is initiated inside the tumour microenvironment through complex communication between these cells and the cancer cells, which often leads to the body's natural immune response being blocked in the vicinity of the tumour. The inflammation can also protect the tumour during treatment. The tumour tissue also contains an inhomogeneous group of immature cancer cells known as cancer stem cells, which continuously progress into tumourigenic mature cancer cells

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The interleukin-1 system

Interleukin-1 circulates in the blood, usually in very low concentrations, and plays a central role in the body's immune defence by stimulating the immune cells [2] and triggering inflammation. Interleukin-1 is important for the body's resistance to, for example, bacterial infections, and induces fever (among other things) through its influence on the central nervous system. The interleukin-1 system is involved in many autoimmune and inflammatory diseases .

Interleukin-1 binds to a receptor complex on the cell surface, which transmit signals that set off a cascade of different inflammatory processes. One component of the interleukin-1 receptor complex is IL1RAP (Interleukin-1 receptor associated protein), Cantargia's target molecule

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One antibody – two potential modes of action

IL1RAP is found on cancer cells in both solid tumours and in leukaemia. It is a central component of the tumour's strategy for creating a 'fertile' inflammatory microenvironment in which cancer cells can proliferate and expand. IL1RAP forms part of the receptor on the cancerous cell used by interleukin-1 to transmit signals. Inside the tumour, interleukin-1 signals between cancer cells and stromal cells, helping the tumour to grow. Cantargia’s strategy is to attack IL1RAP with an effective antibody-based cancer treatment.








The company’s product candidate, CAN04, has two potential modes of action. CAN04 blocks signals from the target molecule IL1RAP, which decrease inflammation and limits tumour growth.  CAN04 also stimulates the natural killer cells (NK cells) of the immune system to carry out a lethal targeted attack on cells that overexpress IL1RAP, a  process called Antibody Dependent Cell-mediated Cytotoxicity (ADCC).

References

[1] Hanahan and Weinberg (2011) Hallmarks of cancer: The next generation. Cell 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013.

[2] Garlanda. C et al. (2013) The Interleukin-1 Family: Back to the Future. Immunity 39, 1003-1018. http://dx.doi.org/10.1016/j.im...