While tremendous strides have been made in the fight against cancer – the battle is far from over. For patients identified with early stage cancer today – the diagnosis is not a death sentence. Some forms of cancer are transitioning from being fatal to chronic conditions, the 5-year survival rates for many forms of cancer have improved dramatically. 

 

For those individuals, and there are many, whose cancer goes undetected until it has reached an advanced stage and spread to multiple organs – modern medicine can do little more than hold back the tide of advancing disease. New treatments and new combination therapies can sustain life but only in very rare cases does it lead to a cure.

 

There has been much excitement of late concerning immunotherapeutic approaches to treating cancer. The innate immune system, the body’s first line of defense against infection, is not effective at fighting cancer because it becomes tolerant to the tumor and no longer recognizes it as foreign. The concept of arming the body’s natural immune system to fight cancer has been around since the 70’s. Back then, it was considered little more than science fiction. However, research continued unabated with the first breakthrough coming in the mid-80’s with the discovery of interleukin, an immune boosting agent. After much trial and error, the first real cure of a late stage cancer patient with an immunotherapy came in 1985. While interleukin can be very effective in a subset of patients with particular types of cancer – it is largely ineffective and the cure rate remains low. However, it was the first real sign that immunotherapy could lead to a cure in such advanced patients. 

 

In recent years, adoptive cell therapy has received much attention from the scientific and medical community as it may be effective in a broad range of cancers. Adoptive cell therapy or ACT involves removing cells from the patient and educating those cells outside the body before re-infusing them back to the same patient. This is known as a personalized medicine – a unique treatment is prepared for each individual patient. 

Various methods are being used to prime the patients’ blood cells to fight against cancer in a vaccine like manner. Methods include selecting and growing the immune cells that naturally react against the cancer. Gene therapy is also used to insert new DNA or genetic material into the patients’ cells to give those cells new properties, such as being able to recognize cancer cells. 

 

Unfortunately, the cancer vaccine field is littered with late stage failures. Early attempts were tested in advanced patients whose immune systems were severely compromised. Todays next generation advanced technologies are leading to more potent cancer vaccines and cell therapies which appear to circumvent the limitations of the earlier attempts. 

 

Dutch company Kiadis is a company with a very promising cell based technology in late stage development. The lead compound, ATIR, is being developed for advanced blood cancer patients in need of a bone marrow transplant but for whom a matched donor is not available. Recently announced, 5-year follow up data from a Phase I/II study demonstrated a 67% survival in ATIR treated patients. This compares very favorably with data from patients who have received a transplant from a matched donor (5-year survival estimates are between 20-35%). ATIR is now being investigated in an international Phase II/III trial with initial data expected in 2015. 

 

Pharmaceutical companies have typically shied away from such personalized therapies. They would much prefer to manufacture drugs in bulk at well regulated and standardized manufacturing facilities. Personalized treatments mean the patient is involved in the manufacturing process – they have to visit dedicated medical centers prior to treatment and cells from the patients have to be sent to specialized processing facilities. It’s complex and expensive. But even large Pharmaceutical companies are waking up to the promise of these immunotherapeutic approaches to cancer which are not just holding back the tide but offer patients new hope and perhaps a real breakthrough. 

 

Another immunotherapeutic approach is to turn on mechanisms within the patients’ immune system to enable it to recognize and fight against the tumor cells or turn off mechanisms within the tumor which help it evade the immune system. The targets of these new therapies are often called immune checkpoints because they regulate the body’s immune system. It is now known that tumour cells co-opt these checkpoints to avoid detection by the immune system. Therefore, unlocking the inhibitory checkpoints of the immune system could be the most effective way of fully harnessing the power of the immune system to fight cancer.

The first such checkpoint inhibitor to reach the market was Yervoy for the treatment of melanoma. The key to the potential for checkpoint inhibitors such as Yervoy and follow up compounds in development is the durability of response. Patients who respond to treatment (about 22% in the case of Yervoy compared to about <9% for conventional treatments) have effective cures or at least a fatal disease is turned into a chronic condition.  

While still experimental – these new treatment modalities are showing impressive response rates, with up to 40% of patients in some early trials showing a complete response following aggressive immunotherapy treatment. In August of this year, recent NASDAQ IPO company, Kite Pharmaceuticals reported unprecedented results from a small 13 patient trial which enrolled patients with different forms of blood cancers. These patients had tried everything and their disease was still progressing. Kite reported that 12 of the 13 patients (92%) had responded to treatment and 8 were in complete remission (60%) – early but very exciting results. 

 

European research is also at the forefront of this exciting frontier of medicine. French company, Innate Pharmaceuticals, is working with Bristol Myers Squibb to develop lirilumab – a monoclonal antibody which acts on a checkpoint within the immune system to prime natural killer (NK) cells (these cells are a type of white blood cell) to recognize and attack cancerous cells. Lirilumab is currently in Phase I and II clinical trials for various forms of cancer. While still early days, the initial results have been very encouraging. 

 

These technologies are promising but need support not only from the medical and scientific community but also from industry partners to help commercialize these treatments and get them to the patients where they can start to make a difference. In the past year, new alliances have been announced between pharmaceutical companies, research centers and innovative healthcare companies to combine resources and expertise. Biotech startup, Juno Therapeutics, which works with several high profile cancer centers in the US to develop immunotherapeutic approaches to cancer, raised an unprecedented $300m of venture financing in the past year and Kite Pharma mentioned earlier, raise $134m in its IPO. The technology developed by French company Cellectis, which utilizes the genetically engineered cells from a single donor to treat multiple patients, has attracted the attention of many potential partners. Pfizer sign a deal with Cellectis earlier this year for $80m upfront and will pay up to $185m per product. Again the amount of capital flowing into these companies underscores the excitement for this new wave of cancer treatments.

 

The main drawback of chemotherapy is that it affects all growing cells indiscriminately leading to terrible side effects. Our new knowledge and understanding of cancer is helping to elucidate the underlying mechanisms of the disease. The hope is that this new information may lead to the development of elegant and precise ways of hitting cancer cells leaving the healthy cells untouched. Our natural immune systems are designed to fight off foreign bodies – bacteria, viruses, unrecognized cells. This system has been fine tuned by evolution though the ages – it seems intuitive to harness this power and direct it against these rogue cells and obliterate them from the body.

 

With such encouraging, though early results, the future for cancer patients looks a little brighter.