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Chris Woolmams
Dendritic cell vaccines and immunotherapy

A review on Dendritic Cell Vaccines, Dendritic Cell Therapy, and Immunotherapy, by Chris Woollams

What is it? 
Dendritic Cell Vaccines, or Dendritic cell therapy, is another ´Alternative´ Cancer Therapy which is felt to be full of promise. Dendritic cells are unique antigen-producing cells, capable of sensitising T-cells to both new and existing antigens. In English that means they help prepare the T-cells so that they can attack the bad guys.

Dendritic cell vaccines are increasingly being used to treat cancer in mainstream hospitals from The Preston Robert Tisch Cancer Center at Duke Medical School in Carolina to Cedars Sinai Medical Center in LA. The treatment, which is defined under the banner of Immunotherapy, aims to increase the body´s immune response against the cancer.
Dendritic cell vaccines (DCVs) are actually a slight misnomer. The idea of a vaccine to most people is something that prevents an illness ever occurring. These vaccines are developed directly from the patients illness, tailoring an immune response to try to kick out that particular cancer.  And Dr. Harmon Eyre, the VP of Research at the American Medical Association has stated his conviction: ´Patients responses are far out of proportion to anything that any current therapy could do´.

Probably the first use of Dendritic cell vaccines was at Stanford Cancer Institute where Dendritic cells (DCs) were isolated from patients with non-Hodgkin´s lymphoma. The DCs were loaded with immunoglobulins from the patients´ cancer cells. After re-injection a significant response was obtained from the T-cells and out of 6 patients, two had a complete response, with complete cancer regression. 

Early Clinical Trials with non-Hodgkin´s lymphoma have taken place while other cancers have also been treated, for example multiple myeloma, prostate, colorectal and non-small cell lung cancer. Stanford say that the treatment ´represents a promising and safe form of immunotherapy´. 
Other forms of Immunotherapy

Dendritic cell therapy represents just one way of stimulating the immune system to act against the cancer. Interleukin and Interferon have been used in hospitals against cancer. But in 2015 Immunotherapy has become a ´hot topic´.

     1. A whole new area of Pharmaceutical research has sprung up over the last 6 or so years - it is called (no joke) Cancer active immunotherapy. For example, 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). One does however wonder ´for how long´ are the tumours going to stay shrunk. Despite Cancer Research´s euphoria, excuse us if we say we´ve heard it all before.

     3. The potentially big win is for a company called Immunocore, who have developed something called ImmTAC and drug companies are flocking to do joint ventures, such is the promise (Click here). Merck have already developed pembrolizumab and Bristol-Myers Opdivo.

Stimulating the immune system 

a) DIY  
I have long argued that one of the biggest failings of the Medical Profession at the time of cancer diagnosis is ignoring the patient´s immune system. People with weakened immune systems have a higher risk of developing cancer. Newly diagnosed patients always have poor immune systems; and the current offerings of surgery, radiotherapy and chemotherapy just make matters a whole lot worse. Such treatments can wipe out your white immune cells and also cause severe damage to your microbiome - the intestinal flora, now clearly established in over 80 clinical trials and 5000 research studies to be essential as the prime directors of a healthy immune system. These friendly bacteria also play a crucial role in making cancer-fighting compounds. Taking multi-strain probiotics is a limited option, but why kill the good guys off in the first place? They were well and truly on your side!
Of course, Doctors regularly monitor your white cell count whilst you are having chemotherapy, but often little attempt is made to differentiate between the many different types of white cell. 

Many people think that they can DIY their immune system and rush to the High Street for a few pots of vitamins. However, these are mostly synthetic and of dubious benefit.  

One of the biggest problems is the ability of cancer cells to actually hide from the immune system. Often (as we have covered in Cancer Watch) this occurs by the cancer negating messages that are crucial to a strong immune system. Or blockages around the core DNA sto messages telling the immune system to develop an appropriate response.
Medical Herbalists know that herbs are potent stimulators of the different aspects of the immune system. Cat´s Claw, Echinacea, Curcuma Longa (turmeric) seem to do a pretty effective job. But herbalist know that it is not enough to stimulate the quantities of the various white cells; the rogue cells need to be lit up for the immune system to see them. Astragalus is one herb that seems to effectively do both jobs increasing the quantity, whilst placing the rogue cells on the immune system radar. It has been extensively studied in cancer centres from Germany to Texas.

But even that is not enough. Recent studies show that you can make more white cells by using herbs and vitamins, light up the rogue cells with Astragalus, but the T-cells produced to attack still need to be activated. Several recent research studies have shown that the first thing the T-cells do is look for a vitamin D molecule and this activates them. Somewhere in this step vitamin K plays a role, but to date no one knows its exact nature.

So, it´s clearly an extremely complex business, and no where near fully understood!

However, amidst all the ´alkalise your body, take curcumin, vitamin D, herbs, avoid glucose and cows´ dairy´ general diet advice comes Gc-MAF (click here). This is a ´natural´ Immunotherapy from a company called Immuno Biotech, that you can buy yourself, and drop into your Complementary and Integrative programme. Gc-MAF is a naturally occurring protein in your body, but in people with cancer it is blocked by an enzyme called Nagalase. So the idea is simple - give people Gc-Maf and by pass the problem. 

Needless to say, this has caused howls of protest from the usual quarters. Immuno Biotech even had their bank account stopped. There is research on it, and it costs only a fraction of the price of a drug.

2) The Medical Route

The Medical Profession have come to the party late. They have previously tried to boost the immune system using synthetic copies of immune-boosting chemicals like interferon and interleukin with mixed and limited success. Again, stimulating the quantities of white cells in the immune system is only a part of the job.

It also doesn´t help that many cancers may develop from stem cells, which are your own normal precursor cells to healthy cells. How would the immune system be expected to identify them? Scientists at the Fred Hutchinson Cancer Research Center in Seattle have identified a protein produced by cancers that actively blocks special helper cells from stimulating the T-cells in the immune system. (The T-lymphocytes chase after rogue cells, as long as they know what to look for). The T-cells thus cannot do their job because the rogue cells haven´t been identified for them and are also present in reduced numbers.
But what if you could actually take the patient´s specific cancer, and their own immune cells and somehow reboot the immune cells to increase the numbers of T-cells whilst also ´helping´ them recognise the rogue cells more easily; thus not just stimulating the volume of the immune cells but the recognition quality too. Can it be successful in generating a response? 
Dendritic cells - what are they?
Dendritic cells are a part of the body´s normal helper immune system, called the Antigen Presenting Cells, or APCs. They constantly sample the environment in the body looking for rogue cells and invaders, and then present a protein combination to the T- lymphocytes in the lymph nodes. This combination is thus specific to the rogue cell. Other helper cells cause the T-cells to become cytoxic (cell destroying), and an army of T-cells is then released from the lymph nodes looking for, and binding to the surface of, any cell that has the same specific protein combination.
So Dendritic cells are T-cells´ little helpers. For example, after cell injury following an accident or damage to the tissues, a factor (the DNGR-1 receptor) on a Dendritic cell is activated and this mobilises the immune system to deal with the dead cells. Dendritic cells are the alarm; the early warning system.
In cancer, they don´t seem to work very well because of the protein identified by the Fred Hutchinson Cancer centre above and so their numbers are reduced.
But if the patient´s own Dendritic cells could be harvested from the patient´s own blood or bone marrow, and then multiplied in the laboratory, the theory runs that they would have some recognition of the cancer. To inject vast numbers of them back into the body with the cancer should see the cancer take a serious hit. 
Dendritic cell vaccines and immunotherapy 

Most Dendritic vaccines are produced by fusing the patient´s cancer cells with Dendritic cells from other human donors. The Dendritic cells are loaded up with dying tumour cells, cancer cell RNA and other antigens before injecting them back into the patient. Dr Steinman of the Rockefeller Institute, in his address to the Baylor University Medical School sites two concerns that the loaded cells don´t always provoke a T-cell response (something that Stanford in their work with non-Hodgkin´s have also found); and often they do not actually end up in the lymph nodes (the place where the T-cells multiply rapidly if stimulated). He sees more potential in trying to coax the Dendritic cells currently inside the body to take up cancer cells. This he does by making cancer cell vaccines and trying to upload them into the Dendritic cells; the Dendritic cells are known to have large numbers of receptor sites on their surface.
Joseph Baar of the Pittsburgh Cancer Institute reviewed Dendritic cell vaccine developments as long ago as 1999 in the Oncologist magazine. Clinical trials were originally developed for melanoma but have been extended to other cancers. 
The work does have research behind it: Since the first clinical trial (Nestle FO, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat. Med. 4 Mar 1998; 4(3):269-70) was published in 1998, the number of clinical trials with Dendritic cell vaccines for various types of cancer has been increasing rapidly worldwide.  Provenge is a Dendritic Cell Vaccine from Dendreon with FDA approval for use with prostate cancer patients - we cover it in our drugs section. However it does had side effects and Clinical Trials show it extends life by a mean 4 months, but for some, considerably longer. Go to our A-Z guide to drugs to find out more.

There are also private options:                                                                                    
The Issels Clinic currently uses a method of dendritic cell production and administration following the model pioneered by Richard L. Edelson and Carole L. Berger of Yale University. This painless procedure is also called transimmunization.
Most treatments are, however, private and thus the patient is reliant on the quality of the particular clinic. And the patients own financial status.

In the UK, The Dove Clinic offers this therapy.

Our ´bottom line´

(Chris Woollams) If you read the former Royal Marsden´s Professor Mike Brada and his interview on future treatments for brain tumours in icon and on this website, he talks of the complex genetic understanding for Dendritic Cell Vaccines and how it is really improving. He says that the brain does not have many dendritic cells and so new, extremely clever and complex ways of working are being developed. But in fact, the Preston Robert Tisch Center at Duke Medical Center in Carolina used it experimentally with brain cancer patients more than 10 years ago for brain tumour patients. 

This leads to my concern. Dendritic cell therapy has experts who are fans and, of that there´s no doubt. But, it seems inexplicably, it simply does not work with quite a large number of people. False hope is thus something to avoid, especially if coupled with the expense of private treatment. It all seems very clever, but early days and a bit ´hit or miss´. Indeed, I have read reports that say that you can prepare the correct rogue cell/dendritic cell combination and put it back in the patient but get poor uptake from the T-cells in the lymph nodes. Perhaps I am wrong; perhaps the launch of Provenge proves me wrong. But, as yet there don´t seem to be the strong and robust Clinical Trials orthodox medicine normally demands, yet treatment in Hospitals and cancer clinics goes ahead.

Overall, there´s no doubt Immunotherapy is flavour of the year. We will see how it develops. And if Gc-MAF´s research can compete. It only has to knock the tumour back for a short while in 50% of cases, and make it disappear in 7% of cases and penny for penny, it will be a much better offering that the new drugs coming on stream. As leading skeptic Professor David Colquhoun of UCL said on TV´s Newsnight "The problem with many of the new drugs, is that they just don´t work very well". We shall see.

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