Cancer

A global challenge

Cancer is one of the most common causes of death, accounting for around 20% of deaths in the western world. Globally, 14 million people are diagnosed with cancer each year, of which more than eight million die from the disease [1]. Cantargia’s CAN04, one of the new treatments emerging within the field of immuno-oncology, has a large potential in this area.

Despite considerable progress in the treatment and diagnosis of cancer, there is still a huge need for new treatment methods. Cantargia’s clinical development will initially focus on non-small cell lung cancer (NSCLC) and pancreatic cancer since the system attacked by CAN04, through interleukin-1, has an important role in their development and since Cantargia’s own research has shown high levels of IL1RAP on these tumours. However, CAN04 also has potential for treatment of several other types of cancer, including leukaemia [2,3] , within the immuno-oncological platform. Evaluation of CAN04 in combination with other therapies will also be of great interest.

Lung cancer

Globally, there were 1.8 million new cases of lung cancer confirmed in 2012 [4] and more than 1.5 million deaths as a result of lung cancer. Of all cancers, lung cancer is responsible for the highest number of deaths and is the fifth most common cause of death after cardiovascular diseases, stroke, COPD and respiratory infections. Lung cancer is difficult to treat and requires significant medical resources due to the large number of people affected. Lung cancer is primarily treated with a combination of surgery and radiation or chemotherapy, but also with targeted treatments such as antibodies against PD-1 and PD-L1, which stimulate the immune system. The survival rate after five years remains below 20%, however. Promising results from studies at the MD Anderson Cancer Center in the USA have been reported using antibodies that block interleukin-1 [5]. A reduction in the amount of inflammatory biomarkers was observed during these studies, which could be very valuable in the treatment of tumours, as well as for improving the quality of life of patients. In other studies, Interleukin-1 has also been proven to play an important part in spreading lung metastases [6,7].

Pancreatic cancer

Pancreatic cancer is a disease difficult to treat due to late diagnosis, it is often discovered at a point when it is hard to surgically remove the tumour and the cancer already has expanded to other organs. Pancreatic cancer affects 178,000 people each year, of whom 173,000 die [4] and the five-year survival rate is only approx. 7%. Pancreatic cancer is currently treated with a combination of several chemotherapies, but also with radiation and surgery wherever possible. Thus, there is an urgent need for new treatment methods. Pancreatic cancer is disease in which inflammation plays a significant part in the tumour growth, and where interleukin-1 signalling has been observed to be of importance [8,9].

AML (acute myeloid leukaemia)

AML is the most common form of acute leukaemia in adults and is characterised by a quick increase in white blood cells, which accumulate in the bone marrow and disrupt the production of regular blood cells. The disease progresses quickly and patients die within months if left untreated. The underlying cause of the disease is genetic damage. There were an estimated 18,000 new cases in the USA in 2014, 10,000 of which led to death [10]. No major progress has been made in the treatment of AML over the past few decades. Cytotoxic drugs, the most common form of treatment at present, are known to have a low level of effectiveness and severe side effects. 


Referenser

[1] http://www.who.int/gho/mortali...

[2]  Acuner Ozbabacan, S.E. et al. (2014) The Structural Pathway of Interleukin 1 (IL-1) Initiated Signaling Reveals Mechanisms of Oncogenic Mutations and SNPs in Inflammation and Cancer. PLoS Comput Biol 10(2): e1003470. doi:10.1371/journal.pcbi.1003470

[3] Dinarello, C.A. (2010) Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev 29:317-329. Doi 10.1007/s10555-010-9229-0

[4] Globocan 2012 http://globocan.iarc.fr/

[5] Hong, D.S. et al. (2015) Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer. Invest New Drugs 33:621–631DOI 10.1007/s10637-015-0226-6

[6] Wang et al. (2014) IL-1b-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumourigenesis Cancer Res; 74(17)

[7] Carmi, Y. et al. (2011) Microenvironment-Derived IL-1 and IL-17 Interact in the Control of Lung Metastasis J Immunol 186:3462-3471; doi: 10.4049/jimmunol.1002901

[8] Wörmann, S.A. et al. (2014) The immune network in pancreatic cancer development and progression. Oncogene. Jun 5;33(23):2956-67. doi: 10.1038/onc.2013.257.

[9] Tjomsland V. et al. (2011) Interleukin 1α Sustains the Expression of Inflammatory Factors in Human Pancreatic Cancer Microenvironment by Targeting Cancer-Associated Fibroblasts Neoplasia. 13(8):664-75.

[10] http://www.cancer.org/acs/grou...

[11] Järås M, et al. (2010) Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. PNAS 107(37) 16280-16285; doi:10.1073/pnas.1004408107

[12] Askmyr et al. (2013) Selective killing of candidate AML stem cells by antibody targeting of IL1RAP Blood 121: 3709-3713

[13] Ågerstam, H. et al. (2015) Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia PNAS 112 (34) 10786-10791; doi:10.1073/pnas.1422749112

[14] Ågerstam H, et al. (2016) IL1RAP antibodies block IL1-induced expansion of candidate CML stem cells and mediate cell killing in xenograft models. Blood (prepublished 12/9-2016); doi: 10.1182/blood-2015-11-679985


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