Saturday, 8 February 2020
Author: Mr. Peter Schwegler, CH-8703,
Erlenbach, Switzerland- Journalist and cancer patient.

Dear family, friends, acquaintances and relatives

Recently was the international cancer day. The prognoses issued by the WHO are alarming. Currently, about 18 million people are diagnosed with cancer every year. In the future, doctors warn that this number is likely to increase significantly. The reasons are different.

According to a new prognosis of the World Health Organization (WHO), the number of cancer cases worldwide is expected to almost double by 2040. This is according to the World Cancer Report of the International Agency for Research on Cancer (IARC), which is updated every five years.

According to this report, 18.1 million people worldwide will be newly diagnosed with cancer in 2020, and 9.6 million people will die of it. In 2040, about 29 to 37 million people are expected to be newly diagnosed with cancer, says the IARC reports on World Cancer Day. One reason for this is the increasing life expectancy.

Cancer types vary by country

The most common cancer type worldwide is lung cancer, followed by breast cancer and colon cancer. Lung cancer is also the most common cancer cause of death, ahead of colon and stomach cancer. The frequency of cancer types can vary greatly from country to country.

Surviving cancer is also a question of prosperity, according to the agency, which is part of the WHO. Those affected in poorer countries as well as poorer sections of the population in rich countries have a lower chance of survival.

The likelihood of dying of cancer in high-income countries fell by 20 percent between 2000 and 2015, and by only 5 percent in low-income countries.

Diverse reasons

The fact that in high-income countries, lower earners are more often affected by cancer than higher earners is due to many factors, the report goes on. These include differences in smoking habits, alcohol consumption, diet, obesity and physical activity. Those on low incomes often went to the doctor later and missed an early diagnosis, which makes a cure more unlikely.

But I think it’s also because we are very dependent on the Pharmaceutical Industry today, and therapies, no matter how successful they are, will not be supported if they don’t fit into the profit motive of big pharma. These include photodynamic therapy and laser therapy. Even the therapy with dendritic cells, for which the Nobel Prize in Medicine was awarded in 2011, is not yet fully established despite more than 7000 scientific publications which included more than 4000 patients. Cancer therapies with dendritic cells has proven to have incomparably higher success rates than, for example,  therapieswith pharmacologically controlled chemo.

In the following interview I would like to introduce this therapy to you. The interview with Professor Frank Gansauge from Ulm was very instructive. Of course, I couldn’t resist asking him about the reasons for the, in my opinion, low level of awareness of the therapy and the connections to big pharma. The answers are not really surprising. But read them for yourself.

Best regards and until next time

Peter

Interview with Prof. Dr. Frank Gansauge,MD, Ulm, Germany

 

The dendritic cell therapy (DCT)

By: Peter R. Schwegler

Professor Gansauge, what is the idea behind a therapy with dendritic cells?

The idea behind it is a kind of vaccination against cancer outside the body. The body’s immune system often doesn’t recognize the cancer. Cancer cells can hide from the immune system. Therefore, certain cells are helped in the laboratory to recognize the cancer cells and destroy them. This happens, so to speak, under optimized conditions and so we can vaccinate against cancer.

What exactly are dendritic cells?

The term dendritic cells are actually the description of the cell form. Dendritic cells under the microscope have many feet and branches. This form has given dendritic cells their name. Scientifically speaking, it is a CD86 positive cell.

What experience with dendritic cell therapy in cancer we have today?

The experience now spans over the last 20 years and includes over 7,000 scientific publications and more than 40,000 patients. It shows that a therapy with autologous dendritic cells is a very effective therapy with very few side effects, i.e. almost no side effects. Patients may develop a slight fever on the day of vaccination. More has not been observed so far. In the palliative area, i.e. when the tumour could not be removed and has remained in the patient, we have response rates of 60 to 65 percent, depending on the type of cancer, according to WHO criteria. In adjuvant therapy, i.e. the prophylactic use of immunotherapy to prevent further metastases, the success rates are considerably higher. In the case of rectal carcinoma, for example, we were able to reduce the recurrence rate from 45 percent to 11 percent.

At what stage does dendritic cell therapy make sense?

A dendritic cell therapy makes sense at every stage. We use it at every stage. Of course, I prefer adjuvant patients, where the therapy only must be applied once and then, based on the follow-up examination, they tell me that everything is fine. The patients with adjuvant therapy are also the ones where we have the most success with this therapy, because here a cure can be achieved.

Peter Schwegler discussing with Prof. Dr Gansauge

Are there differences in the composition of cells within the individual tumour cells?

A tumour is always a very heterogeneous history. It always contains different types of cells. Even the cancer cells do not consist of one clone, but it is always a variable of cells.

Cell therapy with dendritic cells, is there a limitation?

In the literature today you can find dendritic cell therapies or studies for almost all types of cancer. Recently there was even a publication on the treatment of acute myelinic leukemia. Even for this indication dendritic cell therapy is now used. The success rates among the different research groups and authors are very comparable, generally around 60 percent. The response rates are defined and confirmed by technical examinations, i.e. by computer tomography such as PET or MRI.

Why do we usually talk about vaccination and not about cell therapy?

The term vaccination has become common in the context of this therapy. This is since people are basically considering whether this therapy can be used prophylactically against cancer. However, it should be borne in mind that this cell therapy is only twenty years old and has so far been used almost exclusively in palliative situations – late stage IV. However, in order to examine whether dendritic cell therapy has a prophylactic effect, a long-term study would have to be launched with a duration that we would probably not live to see the end of. In general, I can say that it has little to do with vaccination, but it is what it is called. One should talk about dendritic cell therapy and not about a vaccination.

How many applications of dendritic cell therapy are necessary for the desired therapeutic success?

In the adjuvant situation, a one-time therapy after the operation is sufficient. The situation is different in the palliative situation. Here the therapy must be repeated several times. The reason is that we immunize against the snapshot of the cancer. However, the cancer cell is a rather disordered cell, which is also constantly changing. You can see this in conventional therapy as well. For example, the cells respond to chemotherapy once, then again not. The cancer changes and we can hardly immunize against what is there in four months. That is why sometimes it is necessary to repeat the therapy after six months, for example. But this must be decided individually, i.e. from patient to patient.

Is there also the possibility of a cure?

Yes, there is. There are amazing healings even in incredible situations. I would like to refrain from putting these cases in the foreground and give the patients false hopes. I like to explain this based on clinical studies. Of course, there are always a few very happy patients who are cured. But as a serious physician I cannot make any promises based on these patients alone.

Are there patients who do not respond to this therapy at all?

Yes, of course there are. At a response rate of 60 to 65 percent, the therapy does not work at 35 to 40 percent. Anyone who makes a hundred percent cure promise in cancer therapy today is simply lying. In chemotherapy, we speak today of successful with a 30 percent response rate.

Prof. Frank Gansauge during his lecture in Zurich, January 2020

What is the situation with patients who are already undergoing therapy, for example chemotherapy, or therapy with checkpoint inhibitors?

These therapies can be combined with dendritic cell therapy without any problem because we are attacking from a completely different side. The fight against cancer can be explained very well in military terms. If you want to win the war, you need not only the air force but also artillery, infantry and navy. I like to refer to chemo as artillery and air force. We, however, are the infantry. The dendritic cells are the officers who go into the lymph nodes and train the soldiers there, the cytotoxic T lymphocytes.

 

What is the difference between CAR T-cell therapy and dendritic cell therapy?

It is a completely different principle. To stick to my comparison, they use the soldiers, the T-cells, for that. These cells are genetically modified. Therefore, this therapy, in contrast to dendritic cell therapy, is also afflicted with severe side effects. It should also be noted that this is a very difficult product to control. Dendritic cell therapy is a therapy that is regulated on a higher level in the algorithm. This means that I have a further regulator which I do not have in the artificially propagated T-cell therapy.

How do you view the fact that Novartis has failed in its attempt to patent the CAR T-Cell therapy and has withdrawn the patent application?

The idea of priming T-cells is not that new. These methods have been around since the 1990s. It is always a question of replenishment. This is another reason why I am personally a friend of dendritic cells. A dendritic cell can prime, let’s say, about 1000 cells per day and thus create a continuous supply of these cells. I do not have this continuous effect with all the other therapies, i.e. via the effector or T-cells. Therefore, a permanent supply must be provided. If we compare it with chemotherapy, today there are pumps that apply the substance over several days and thus have far fewer side effects than if they infused everything at once.

Where do you see the importance of dendritic cell therapy in the future?

I am honest with you, I don’t know. The idea is good, and the results are excellent. Nevertheless, there are ideas that are very good and successful and yet have been kicked to death. The interest of the pharmaceutical industry with its centralized structure certainly plays an important role. We know the system from the manufacturer to the wholesaler to the pharmacist or hospital. This is not possible with dendritic cells. I can still remember well when we presented our laboratory to the public in 2002, a pharmacy wanted to order ten packs of dendrites. Of course, this is not possible and this decentralized structure, which is necessary here, the whole pharmaceutical industry is not prepared, not even for individual production.

Professor Gansauge, thank you very much for the interesting conversation.

Dendritic cell therapy

Still the first choice of cancer therapy is surgery. This is an attempt to surgically remove the primary tumor. After the surgery, chemo- or radiotherapy are often used as prophylaxis. An attempt is made to destroy any remaining tumour cells. Only the metastases are not attacked, but only the primary tumor.

Why not use immediately an immune therapy with dendritic cells.

This therapy has few side effects and has been used for years (first cancer vaccination in 1996) in numerous clinics and by renowned doctors worldwide. Studies in the early years of 2003 at the Charité in Berlin already proved a high immunostimulatory effect. Already from Moldenhauer et.al. 2003-2017 and at the Institut Pasteur (Vuillier et al 2001) the high clinical effective therapy application was proven.

The therapy with dendritic cells

Since the Nobel Prize in Medicine for Dr. Ralph Steinmann in 2011 for his discovery in 1973 and its potential in the treatment of cancer, there have been over 100,000 scientific publications, studies, dissertations and press releases to date. All of them prove the effectiveness and impact in cancer therapy with dendritic cells and point to the success of the therapy.

A dendritic cell therapy with one to several application cycles can be performed at any stage of the disease. Since it has hardly any side effects, it can also be combined with other therapeutic measures, whereby positive effects can occur. (For example, pain-relieving drugs could be dosed less or even discontinued). The following positive effects of dendritic cell therapy have been scientifically proven:

  • Improvement of immune competence through Th1 cell activation
  • and tumor priming
  • Increase of killer cells (NK cells in the immune system)
  • -Release of Interleukin-12
  • -Increase of cytotoxic T cells

Targeted immune activation via APC cells with tumor material increases tumor destruction. The tumor cells are increasingly led into apoptosis (cell death). The mean survival time can be significantly prolonged in patients with advanced tumor types, even a complete remission cannot be excluded. Complete remission after treatment with dendritic cells has been observed in many cases. Due to these biological effects of dendritic cell therapy in tumor diseases and metastasis formation, its application is also indicated in the palliative therapy situation.