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A paradigm-shift in cancer?

Immunotherapy is the 2016 Clinical Cancer Advance of the Year and a promising new strategy for treating cancer. But how far have we come?

The American Society of Clinical Oncology (ASCO) justified this year’s choice of Clinical Cancer Advance, immunotherapy, by the fact that no recent advance has been more transformative, particularly over this past year. These new therapies are transforming patients’ lives as well as opening exciting avenues for further research. It could control tumor growth and have fewer side effects than chemotherapy.

So what is cancer immunotherapy? In short, it means a cancer treatment designed to boost the body’s natural defenses to fight the cancer in the body. The techniques and the knowledge and understanding of cancer immunotherapy have grown over many years (the concept dates back to the 1970s) and today two main approaches are being explored. The first approach involves unleashing the body’s natural immune response to cancer and the second approach helps the immune system find and destroy cancer cells. Immunotherapy can be divided into different types, for example therapeutic cancer vaccines, monoclonal antibodies, checkpoint inhibitors and cytokines.

Melanoma and lung cancer

A lot of progress has been made. Newly approved immunotherapies have increased treatment options and improved the patient’s odds for a variety of tumors, while also allowing many with cancer to avoid, cut back on, or delay chemotherapy. Last year the FDA approved two new immunotherapy drugs and more than half of the current cancer clinical trials include some form of immunotherapy. There is also a growing number of individual company- and cooperative group sponsored trials being conducted for all major tumor types.

Novel therapeutics that stimulate the patient’s own immune system has especially revolutionized melanoma and smoker’s lung cancer treatment, two cancer types that occur due to environmental exposure that results in lots of mutations occurring in the DNA of exposed cells. These mutations in turn lead to the production of many aberrant proteins, which are usually recognized by the immune system as potentially dangerous, and any cells that contain these are quickly marked for destruction. These malignancies are called “hot tumors” and they need a long time to figure out how to shield themselves from the immune system. The strategy for these cancer types is that monoclonal antibodies interfere with the ability of the cancer cells to fool the immune system into ignoring them, which is known as checkpoint blockade. This approach hit the spotlight with the successful melanoma treatment of former US President Jimmy Carter, which included a regimen of immunotherapy, radiation therapy and surgery.

Personalized therapy

Cancer immunotherapy is not yet however as widely used as chemotherapy, surgery and radiation therapy and there are a few hurdles to overcome. One of these hurdles is making these therapies work on many patients and thereby understanding why some patients get better and some don’t. Scientists are also looking for ways to predict who will respond best to certain immunotherapy regimens, what is the best way to kick the immune system into action and is there a way to make the treatments less dangerous or expensive?

Nordic progress

During the seminar Cancer Immunotherapy – the universal cancer weapon? at this year’s NLSDays, progress in the Nordic region was among other things highlighted. The CEO of the Norwegian company Ultimovacs, Dr. Øyvind Arnesen, was one of the speakers. His company’s lead product, UV1, is a therapeutic vaccine; a synthetic peptide vaccine directed against human telomerase, currently in three clinical trials. Two of these are documenting safety and the ability of the vaccine to activate the immune system against cancer cells expressing the hTERT fragments that are the components of the vaccine when given as a single treatment. The third trial is assessing safety and clinical outcomes when combining UV1 with ipilimumab in patients with malignant melanoma.

The spotlight was also turned on a Nordic innovative approach by Professor Karl Johan Malmberg at Oslo University Hospital and the Karolinska Institute. He has developed a technique of expansion of adaptive NK cells for cancer therapy. His group studies the molecular and cellular basis for NK cell differentiation and repertoire formation in health and disease. He wants to gain insights into how killer cell immunoglobulin-like receptors (KIR) influence the function of human NK cells. The group is examining the dynamic shaping of human NK cell repertoires during viral infection, tumor transformation and following stem cell transplantation. They are also seeking to implement new insights into the adaptive-like behavior of NK cells in the next generation of NK cell-based immunotherapy for patients with refractory or relapsing malignancies.

Another Nordic company that has come a long way with the strategy of a cancer vaccine is Vaccibody, currently testing its first lead product in a clinical phase I/IIa study. Vaccibody vaccines consist of three modules, each of them serving a crucial purpose to increase efficacy. They can easily be optimally designed for a given disease based on Vaccibody’s expertise within advanced immunology. Their technology platform is versatile and the vaccines can be delivered as DNA, RNA or protein.

This year’s King Olav V’s Cancer Research Award was also awarded to progress in immunotherapy. Professor Kjetil Taskén at the University of Oslo and the Director of the Biotechnology Centre and the Norwegian Centre for Molecular Medicine (NCMM) received the award for his work in immunotherapy.

There is still for certain much more, both progress and setbacks, to come in the field of cancer immunotherapy. Hopefully we will be able to better tailor cancer care and improve or even cure the disease. One of the newest advances is the NIH approval of a human study using a CRISPR-Cas9 to help augment cancer therapies that rely on enlisting a patient’s T cells.

“Cell therapies [for cancer] are so promising but the majority of people who get these therapies have a disease that relapses,” said study leader Edward Stadtmauer, a physician at the University of Pennsylvania in Philadelphia, to Nature. “Gene editing could improve such treatments and eliminate some of their vulnerabilities to cancer and the body’s immune system,” he says.

 

 

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