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Cancer Active Immunotherapy Review

Cancer Active Immunotherapy Review - the new frontier 

Active Immunotherapy is a hot topic, with PD1 drugs like nivolumab, pembrolizumab, and ipililumab leading the way, and CAR-T immunotherapies not far behind and showing enormous potential. Then there are immunotherapy vaccines. Oncologists believe this to be the fourth leg of orthodox cancer treatment. 

We shall see. Over-claims, as usual, are everywhere. But no one can deny that immunotherapy is the new frontier in medicine. 

Unfortunately, not all is rosy, with increasing reports of severe side-effects and risks of diabetes and even death, especially with the combination ´double hit´ immunotherapy treatments being used.

Boosting the immune system to recognise the cancer

The basic idea in Active Immunotherapy is to boost a person’s own immune system, not just in quantity, but tailored to fight their specific cancer so it ´recognises´ the cancer. Of course, there´s nothing particularly new or revolutionary in this idea at all; herbalists believe they have been doing this for years. The excitement is being generated because, for the first time, scientists claim to have developed drugs to do it! Expensive drugs at that; and drugs that can be used Integratively (that is alongside your existing expensive drugs).

The claim is also that these drugs that can increase survival times from a few months currently to a couple of years.

Memorial Sloan Kettering Cancer Center´s expert in Immunotherapy, Jedd D. Wolchok MD, PhD, detailed the future in Scientific American in 2014. "While mainstream drugs will attack the tumour, immunotherapy may be used alongside to get the immune system to refocus and help. In this way, melanoma drug ipilimumbab has increased survival times from just seven months to over three years in 20 per cent of patients". (Actually, that´s not quite true, see data below.)

The anti-PD1 immunotherapies - Pembrolizumab and Nivolumab

This is the new area of excitement. A host of top Pharma companies have rushed to strike deals with biotech company Immunocore.

The common interest was Immunocore´s Immune Mobilising Monoclonal T-Cell Receptor against Cancer (ImmTAC).

Current leaders in the field are Merck & Co, which has an anti-PD1 antibody Pembrolizumab and Bristol-Myers Squibb, which has an anti-PD1 drug Opdivo (nivolumab).

They all work by blocking a protein ´PD1´. PD1 is found on certain immune cells and stops them from recognising a cancer cell. Dr. Jan Lundberg, president of Lilly Research Laboratories, commented on the company´s confidence in cancer immunotherapies.

"The major goal and challenge of cancer immunotherapy is to direct the immune system to recognise and destroy cancer,” he said. “We believe Immunocore´s ImmTAC platform has the potential to do just that.”

New breed of immunotherapies remove the ´checkpoints´

A phrase you will hear a lot is that ´cancer hides from your immune system´.

Another is that ´immunotherapy removes the brakes or ´checkpoints´ that keep T-cells from recognising and attacking cancer cells´.

´Checkpoints´ is the new buzz word.

The origins of the current wave of euphoria started in the early 2000s when clinical trials with melanoma, prostate, renal and ovarian cancers took place. By 2008 there were two CTLA-4 monoclonal antibodies in the game - tremelimumab (Pfizer) and one other (from Bristol-Myers Squibb), both showing a potential to give up to 4 years extra life to 20 per cent of patients (it was claimed). By 2010 the rival, ipilimumab, became the first drug ever shown to extend survival for patients with metastatic melanoma in a large phase III trial. 

According to the research, Ipilimumab reduced the risk of death by 32% and nearly doubled the likelihood of patients surviving to 1 and 2 years, with some patients experiencing ´complete and durable clinical regressions´. 

Based on these results, ipilimumab (Yervoy) was approved by the FDA as first-line therapy for advanced melanoma in 2011 (particularly for melanoma that cannot be surgically removed and is not responding to other drugs.

To quote from the press release: ´Ipilimumab is a type of immune drug known as a checkpoint inhibitor. These treatments work by targeting molecules that serve as checks or blocks on the immune system stopping it doing its job´.

CAR-T immunotherapy

At the end of January 2016, two rival research groups rushed to get their Press Releases out first on another line of immunotherapies. Fred Hutchinson Cancer Center in Seattle, and the University of Pennsylvania´s Abramson Cancer Center have both been extracting T-cells from patients (cells in the immune system that attack the bad guys) and then genetically modifying them with chimeric antigen receptors (CARs) so that they targeted a protein on the surface of the cancer cell. Result? a CAR-T cell that seeks out cancer cells. 

Professor Stanley Riddell of Fred Hutchinson and his team developed their CAR-T to attack the CD19 protein on B cells in leukaemia and lymphoma. In patients who were terminal with just five months to live, remission was achieved in 90 per ken with just a single dose of the CAR-T, a result Riddell described as ´Unprecedented´. However, a number of patients had to be hospitalised and two died because the reaction was too strong. Early days yet.

Immunotherapy for all cancers

Of course, there is little reason to restrict the immunotherapy drugs to any single cancer. Why wouldn´t nivolumab work on another difficult to treat cancer?

Sure enough, in March 2015 the FDA approved Opdivo (nivolumab) to treat a type of advanced lung cancer squamous non-small cell lung cancer, which has grown after patients used platinum-based drugs.

The euphoria was elevated because the drug performed extremely well. Tested in clinical trials against docetaxel, the immunotherapy group lived on average 3.2 months longer. We will come back to this.

In a second, safety trial, where everybody took nivolumab, 15 per cent of recipients saw their tumours shrink or disappear altogether.

A further phase I/II trip by Medarex on prostate cancer patients showed similar results.

In a further study, this time of 582 patients who were known to exit a certain protein, the immunotherapy treatment showed an average of 17.2 months increased survival versus just 5.6 months for the docetaxel.

Immunotherapy - a "double Hit"

Dr. James Larkin is a medical oncologist at the Institute of Cancer Research and a consultant oncologist at the Royal Marsden. He has been part of a team studying the simultaneous use of two different types of immunotherapy - ipilimumab and nivolumab - in a 945-patient trial. The trial recorded in June 2015, that the cancer (melanoma) failed to advance for more than one year in 58 per cent of patients. In all these cases the tumour shrank, or at least failed to advance.

Where just ipilimumab was used on its own, the figure fell to 19 per cent, and then only for 2.5 months on average.

Dr. John Wagstaff at the University of Swansea Medical School has been getting promising results with the double hit´ immunotherapy drugs and kidney cancer. Meanwhile Larkin has now moved on to testing radiotherapy with immunotherapy.

Warning

There are some concerns creeping in about heart problems and even death, associated with the new immunotherapy drugs.

Immunotherapy vaccines

We have an article elsewhere on this website about the immunotherapy Dendritic Cell vaccine, which is full of potential but so far only seems to work in about 15 per cent of cases. But perhaps the greatest excitement comes from Cuba. There, faced with isolation, the regime built their own thriving drug industry - and in 2015 there was a rush to work with CIMAvax, an immunotherapy vaccine showing great promise with non-small cell lung cancer. Roswell Park Cancer Institute are leading the US clinical trials on the vaccine. The vaccine targets Epidermal Growth Factor (EGF) protein, and thus could be used against any cancer where the development of the cancer were linked to this protein.

Cancer Immunotherapy and the need for gut bacteria

One of the early problems with Cancer Active Immunotherapy as it is called, has been that it seems to work very well in just a few people. So often, less than 20 per cent of people with a certain cancer benefit.

Early clues came from research by Lille Medical School, France where it was noted that Bifidobacteria helped ipilimumab work. But - the use of ipilimumab creates the side-effect of damaging these gut bacteria. The Mayo Clinic is teaming up with Evelo Biosciences to test two gut bacterial ´formulations´. It is thought that an immunotherapy drug PLUS gut bacteria could yield greater success.

Alternative immunotherapies?

     1. Nottingham Trent University in the UK is about to go to clinical trials on a new vaccine that they believe will stop prostate cancer growth (Click here).

     2. The first bladder cancer drug for 30 years shank 50 per cent of tumours and made the cancer disappear in 7 per cent (Click here) of cases. One does however wonder ´for how long´ are the tumours going to stay shrunk. Despite Cancer Research UK´s euphoria, excuse us if we say we´ve heard it all before.

     3. German researchers led by Dr. Ugur Sahin of Johannes Gutenberg University, Mainz have been targeting specific mutations around the DNA in tumours. These changes make the cancer vulnerable, and are absent in healthy cells protecting from attack. The vaccines developed don´t just stimulate T cell attack, but the whole immune system. The vaccine has been successful in a variety of hard to treat cancers in mouse models. 

     4. Nascent Biotech, Inc, is the developer of two immunotherapies: Multipharm and Pritumumab. 

Multipharm is a ´platform technology´ that makes use of multiple agents, like antibodies and cytokines. It is also being considered as a potential therapy for organ transplantation and various autoimmune disorders.  

Pritumumab uses a natural human antibody to treat brain cancer and has already been through Phase I and II clinical trials. It is claimed to increase survival rates by 25 to 30%. As always, I´m not sure whether their survival rate definition, is the same as yours or mine.

     5.  GcMaf - this is a naturally occurring protein in the body which kicks macrophages into action. But many cancers and viruses produce Nagalase which blocks this action. Answer? Add lots more Gc-Maf into the body. It´s a natural immunotherapy and has Health Authorities extremely hot under the collar because they say it is being used without perfect clinical trials. Fans argue that it´s a conspiracy to stop a natural cheap compound progressing rather than the expensive drugs (Click here for more info).

     6. Rigvir - This is an oncolytic, non-pathogenic virotherapy which has been used in immunotherapy since 2004. The compound is approved for use by the Latvian, and by the Georgian Government Health Authorities particularly for melanoma, but does seem to have a more general effect. It is also used in some German and Mexican Clinics. A recent Clinical Trial reported in October 2015 was well up to Western standards and reported clear increased survival times.

      7. A small aspirin - cancers produce a molecule called PGE2 and this blocks the ability of the immune system to see them. A small aspirin has been shown to stop the production of PEG2 by the Francis Crick Institute in London (Click here to read more). So far, research shows that aspirin seems to improve chemotherapy results.

      8. Bifidobacteria - if you want controversy, look no further. It is well accepted that certain probiotics in the gut control the immune system. Feeding them high fibre diets increases their number and research shows this increases immune strength. Now research has shown that taking probiotics (and specifically Bifidobacteria) improves chemotherapy results because they boost immune response. The figures (from the University of Chicago) BEAT THE NEW IMMUNOTHERAPIES (Click here to read more

Immunotherapy, where next?

1. The dominating PR at the moment is for the PD1 drugs - but there are other compounds of potential like the CAR-T group developing rapidly with even greater potential.

2. Immunocore has developed a core compound for rival Pharma immunotherapy drugs. These all seem therefore to work the same way.

3. This PD! attack does work. It extends life for a maximum of a year and a half, at the moment.

4. But it works only on about 20 per cent of cancer patients.

5. It is not clear that people need to take it with there current drugs. Indeed specific clinical trials did not show this.

6. No existing drug can yet be said to be a ´cure´ although it may not be long before developments such as the CAR-T immunotherapies show this potential.

7. There is no doubt these new drugs are extremely expensive and represent a new Treatment category - there will now be a programme to debase all alternative immunotherapies. Follow the money!


                                                **********

The history of immunotherapy

Immunotherapy has come down a long road.

The idea of immunotherapy started early in the 1900s. William Coley, MD, a Memorial Sloan Kettering Doctor realised that some patients suddenly beat their cancers after an infection. Although, at the time being unsure whether this was due to the temperature rise during infection (which led to the exploration of hyperthermia as a cancer treatment) or whether it was the fact that an outside pathogen had stimulated the patient´s immune system (and the invigorated immune system then kicked the cancer out), he decided to experiment. His idea was that he would give cancer patients mild infections using his own pathogens that he called Coley’s toxins. This was in 1920.

While having some success, the world moved on and the era of chemo and radiotherapy was born.

Now cancer scientists are beginning to wonder if he was right on both scores. Localised hyperthermia seems full of potential (for example, HIFU, Ablation, NanoKnife), as does re-stimulating a patient’s immune system.

Then came the drugs. Two examples were Interferon and then Interleukin, dubbed ‘Biological Therapies’. 

Cancer is a failure of the immune system. Under normal conditions, the immune system acts to fight off rogue cells at early stages, but sometimes a cancer slips through the immune net. There can be a number of ways this happens. Blockages may occur at the outset around the cellular DNA, preventing healthy and normal messages being read. The science of epigenetics is working to reverse these blockages. However, cancer may itself produce proteins to disable the immune system’s radar. Or it may slightly alter its own identifying proteins and thus hide. Cancer may also produce proteins to disable the immune system’s attack squadron. 

There is even an ´alternative´ immunotherapy called Gc-Maf that claims to combat low levels of nasalise caused by cancer cells´ action on the immune system.

Interferon and Interleukin are cytokines. Cytokines are signalling proteins produced by white blood cells, and they command certain white cells to go and do their job. So, the basic idea is that injections of these two compounds will re-stimulate certain areas of the immune system, Interferon is used with a number of cancers – from melanoma to kidney cancer. Interleukin seems to be delivering better results and you can find more in our research centre Cancer watch.

Monoclonal Antibodies

The idea here is that you take antigens from cancer cells, inject them into, say, mice and harvest the antibodies. They may then be fused with, for example, melanoma cells, resulting in rapidly diving hybrids. The mice portion is then ‘cleaned’, removing as much as possible if not all, through genetic engineering. The result is a ‘drug which usually has a name ending in  -mab.
They may stimulate an immune response, others may bind to the cancer cell surface, and others interfere with proteins produced by cancer cells helping them take control of the patient’s body.

A variety of treatments

Other scientists have looked at areas such as Dendritic Cell therapy. Dendritic cells in a healthy body identify and then carry samples of rogue cells to the lymph nodes for assessment; this prompts the production of T-lymphocytes which come out in large numbers to attack that particular type of rogue cell.

Unfortunately, to date these ideas have met with only limited and varied success. Phase III clinical trials have been inconclusive.

Another area is that of ‘cancer vaccines’ where vaccines are prepared in the laboratory usually from the antigens on the cancer cell surface. These antigens may be general to cancer cells, or specific to one type. The ‘vaccines’ are then injected back into the body to cause a strong immune reaction.

All of these areas are covered on our website (www.canceractive.com)

The complex immune system

Saying that the immune system is a complex system is probably one of the world’s biggest understatements. And thinking that just one element (drug, herb, or vitamin) might stimulate the whole is a little naïve. For example, apart from dendritic cells, your ´white cells´ include  platelets, granulocytes, T-lymphocytes, B-lymphocytes, macrophages, Natural Killer cells, and a whole lot more. 

Typically a hospital will measure your overall white blood count, but this is being shown to be almost meaningless as even a high count may hide a complete shortage of one type of important cell, as my daughter found to her cost. Fighting a brain tumour with a high white blood cell count, but no NK cells thanks to the chemo, can only have one result. 

If you want to stimulate the numbers of white cells the American Vital study showed the best high street compound to be Grape Seed Extract. It’s an OPC and Pine Bark Extract (which was not in the research) might be even better. Then there is the powerful cur cumin, and herbs such as cat’s claw and Echinacea shown individually in research to have effects on certain white cells. Vitamin E (the total 8 component version of tocopherols and tocotrienols) is another immune system booster. And sleep is a great aid, as your pineal gland produces melatonin which in turn stimulates the immune system.

But the immune system needs to ‘see’ the rogue cells. Polysaccharides are important and help communication between cells (Nobel prizes have been won for this discovery). Typically, medicinal mushrooms lead the way, but apples, pears and whole brown rice also contain useful polysaccharides, as do herbs like echinacea and curcumin. One Chinese herb, Astragalushas a double benefit. It boosts the immune cell numbers and helps ‘light up’ the bad guys. 

But even that’s not enough. Carting off some of the rogue cells to the lymph nodes stimulates massive T-cell production. But before they can attack they need activating. So first they pick up a vitamin D molecule – that’s if you have enough in your blood strem. Harvard Medical School recommends that all cancer patients take 5,000 IUs of vitamin D a day – that´s half a day on the beach in the sun, if you prefer. Finally, somehow, and it is not yet clear, vitamin K helps in the activation process.

The microbiome - controller of the natural immune system

And if that weren´t enough, massive research studies coming from America and Europe are showing that your microbiome (mainly the 90 trillion bacteria in your gut) direct about 85 per cent of your immune system by prompting a reaction from your white cells. Worryingly, research concludes they become ill first, then you become ill. And you cannot become better until they become better. At all times you should ensure you keep your gut bacteria topped up in terms of volume and diversity. In America there is increasing concern from oncologists that their actions with drugs and antibiotics damage your microbiome further.

People reading this article also read:

Dendritic Cell Therapy CLICK HERE

Gc-MAF CLICK HERE




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