Exciting new approaches for cancer therapy

Cancer. A word many dread to hear and has taken so much from so many. However, we are starting to win the fight, and two pieces of research published in recent months can contribute to this battle: DCVax-L and TIL’s (tumour-infiltrating lymphocytes).

First, DCVax-L.

Brain cancer affects an estimated 11,000 people each year in the UK, a staggering 30 people each day, and reduces life expectancy by an average of 20 years. While there are over 120 different types of brain and CNS tumours according to the National Brain tumour Society, the most common are glioblastoma’s which grow from glial cells.

Northwest Biotherapeutics has released early results from its phase 3 clinical trial of its technology DCVax-L, and the results are incredibly promising. The technology utilises the patient’s own immune cells to combat Glioblastoma Multiforme (GBM), which is the most lethal form of brain cancer with tumour recurrence in 7 months and survival rates of only 14.6 months. Clinical outcomes have not improved much over the last few decades for those diagnosed with GBM, but those given DCVax-L experienced tumour recurrence much later and were shown to be living much longer.

So, what is this treatment?

The steps in the process are simple on paper (less simple in practice) and begin with taking tumour samples and separating monocytes (dendritic cell precursors) from the patients’ blood. The monocytes are then exposed to the tumour cells to encourage recognition of the markers/proteins on the tumour cells so they can mount a response. These activated cells are then injected back into the patient to recruit and bestow their knowledge on other immune cells, so they can then recognise and attack the tumour cells.

All the patients underwent the current standard of treatment (surgery, 6 weeks of radiotherapy, and chemotherapy with temozolomide). 232 were then randomly assigned the DCVax-L immunotherapy vaccine and 99 received a placebo. Do not fret, however, any patient that experienced tumour recurrence was offered DCVax-L, so at the interim analysis 86.4% of the participants were then receiving DCVax-L.

What were the results?

The study found that 30% of participants lived for an average of 40.5 months while the longest was over 7 years. Compare this to the 14.6 months average survival with current standard treatment this is amazing!

The substantial genetic and epigenetic differences between patients means that each has a different level of response to the current standard treatment, which acts more as a “shotgun” approach. This treatment is unique to the patient it completely negates this issue, while only 7 patients reported adverse side-effects from the vaccine. This is substantially lower than the side effects from chemo and radiotherapy.

One of the authors, Keyoumars Ashkan, said: “Cautious optimism is welcome in an area where for so long the disease and suffering have had the upper hand.” Although further data is required and more analysis is needed, cautious optimism it is!

Second, TIL’s.

In related positive news, a woman diagnosed with advanced untreatable breast cancer is in complete durable regression after being treated with an experimental immunotherapy. Judy Perkins had advanced metastatic breast cancer, which was found to be non-responsive to all conventional forms of treatment. 2 years after being admitted to the programme she is still in complete regression.

This is another highly personalised therapy and begins with DNA analysis of the patients’ cancer tissue to find mutations that are specific to their tumours. Next, tumour tissue is analysed for T cells (part of the immune system responsible for attacking foreign microbes etc) that are already programmed to attack these specific mutations, which are multiplied and infused back into the patient. The patient also receives immunotherapy drugs, one of which is Interleukin-2 (IL-2) and “checkpoint inhibitors”. Checkpoint inhibitors prevent cancer from hiding from the immune system, while IL-2 stimulates infection-fighting cells to multiply and mature.

22 months on for Judy and there are still no signs of recurrence, which is promising for the other patients with advanced colon, liver and cervical cancer who are receiving the same treatment. Although these results are exciting the research is still very much in its experimental phase, with a low response rate of 15%.

The highly personalised nature of these treatments is a double-edged sword – while it specifically targets the patients’ tumours, it also means it costs more and is more time-consuming than the shotgun approach we currently use. Nonetheless, considering the speed at which techniques are advancing, these therapies could eventually be used to de-escalate toxic therapy for the huge population of patients, providing faster and cheaper ways to carry out the process and found.

These studies provide optimistic avenues to combat not only the types of cancer described in the studies but for other forms. “I’m one of the lucky ones,” said Perkins, with treatment options like these and the numerous others being researched may there be many more.

DCVax-L:                                         https://www.nwbio.com/

Breast cancer study:                     https://www.nature.com/articles/s41591-018-0040-8

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