Cancer diagnostics and therapeutics

Each year many people are diagnosed with cancer, a leading cause of death worldwide. The general feature of all cancer types is abnormal cell growth with the potential to invade or spread to other parts of the body. Normal cells transform into tumor cells in a multi-stage process, influenced by genetic as well as environmental factors. However, due to the diversity within cancer types finding the right diagnosis and treatment can be extremely complex.

Within this program at AbSano we aim to develop monoclonal antibodies which will aid in the global fight against cancer. By recognizing tumor-specific markers, antibodies can be used as diagnostic tools to visualize cancer cells. Alternatively, antibodies have shown their value in therapeutic applications, for example by their ability to interfere with cellular signaling or guide a specific compound to the cancer cell population. At AbSano we have selected several promising targets, for which we believe that specific antibodies would provide valuable diagnostic or therapeutic tools. One of these subprograms involves targeting the tumor as well as its nutrient supply.

To grow beyond the size of 2-3 mm3 a tumor needs to arrange its own vasculature in order to supply the tumor cells with their essential nutrients (2-4). Specifically targeting the process of angiogenesis has therefore been a promising strategy for anti-cancer therapies. Even though promising results were obtained in animal tumor models, translating this approach to the clinic has proven to be difficult (5-7). Research has shown that certain tumors are able to shift towards angiogenesis-independent growth upon anti-angiogenesis therapy (8-10). Especially metastases, which are bloodborne and as a consequence generally grow in organs with a high vessel density, are able to target and utilize the existing vascular bed (vessel co-option) and thereby provide access to essential nutrients (8, 11-12). These results suggest that a combination therapy targeting both angiogenesis as well as co-option might prove a more effective treatment strategy.

Interestingly, the cell surface receptor plexin D1 has been shown to be expressed on tumor cells as well as the tumor vasculature in a mouse model of brain metastasis (13). We believe this receptor is a unique candidate for tumor targeting therapies as plexin D1 was shown to be expressed at high levels in the tumor cells as well as its vessels, but not in unaffected brain vessels.

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