• 07 JAN 17

    Why are Dendritic Cells an Effective Cancer Therapy

    By Robert Gorter, MD, PhD, et. al.

    Robert Gorter is emeritus professor of the University of California San Francisco

     Medical School (UCSF)

    As of 2017, even after the Nobel Prize was Awarded to this Therapy, why are Dendritic Cells as an Effective Cancer Therapy still Ignored or even Ridiculed by some “Scientists”?

    Dendritic Cells (DC) can be compared to policemen of the immune system. DC migrate throughout all inner organs of the body, looking for abnormal (bad) cells. These are usually cancer cells.
    Each human being makes at least 100.000 cancer cells per day which are recognized by DC and if all functions well, all cancer cells have been killed within about 24 to 30hours after the DC recognized the cancer cell and initiated an immune response to kill this specific cell.
    As long as this part of the immune system is functioning adequately, nobody can get clinically cancer. But each human being (and animal for that matter) has a little bit of cancer.
    Many things can go wrong in one’s life and when one becomes too much immunocompromised, the policemen can see less well (as if they need reading glasses) and cancer cells get a chance.

    Dr. Gorter reports:
    “Globally, the business with chemotherapy and radiation is a hundreds-of-billions of Euros (Dollars) industry and a lot of money has been invested and, in return, ten to 25 times more is being earnt. Secondly, pharmaceutical companies, hospitals and doctors alike are making (huge) profits of people who are ill. Hospitals and modern medicine wants you to get or be ill as there would be hardly any health industry left. Therefore, in modern medicine, there is very little money and attention for prevention of illness or non-toxic treatment modalities. Ninety-nine percent of what medical students learn is about disease and standards protocols how to treat with patented medications. Less than 1% of the curriculum is spent on prevention of disease.”

    Paulien de Graaf-Cobelens and Dr. Robert Gorter at the opera in Amsterdam

    Paulien de Graaf-Cobelens and Dr. Robert Gorter at the opera in Amsterdam on November 10th, 2014, to celebrate life after being 6 years completely free of end-stage breast cancer by attending the opera Lohengrin by Richard Wagner. In 2017, 9 years later, after her treatment according to the Gorter Model, Paulien de Graaf is still kicking, living a full life and is completely free of cancer. Paulien is one of hundreds of dying cancer patients who recovered completely and added another 10 to 15 years of their lives in excellent health and spirits.


     

    Dendritic cells (DCs) are central regulators of the adaptive immune response, and as such are necessary for T-cell-mediated cancer immunity. In particular, antitumoral responses depend on a specialized subset of conventional DCs that transport tumor antigens to draining lymph nodes and cross-present antigen to activate cytotoxic T lymphocytes and Natural Killer (NK) Cells. DC maturation is necessary to provide costimulatory signals to T cells, but while DC maturation occurs within tumors, it is often insufficient to induce potent immunity, particularly in light of suppressive mechanisms within tumors and the usual chemotherapy and radiation. Bypassing suppressive pathways or directly activating DCs can unleash a T-cell response, and therapeutic targeting of DCs continues to hold translational potential both as a single therapy as in combinatorial approaches.

    The originally Dutch physician Dr. Robert Gorter at his desk in his clinic in Cologne in Germany. From 1986 to 2012, he was professor at five universities in three continents

    Antigens are engulfed by endocytosis by various routes, including receptor-mediated uptake, and are degraded in endosomes by proteases (right). MHC class II molecules enter the MHC class II loading compartment (MIIC) at the limiting membrane. The invariant chain (li), which acts as a ‘pseudopeptide’, is degraded by cathepsins, except for a small fragment (CLIP), which fills the peptide-binding groove of MHC class II molecules. In the internal vesicles of the MHC class II loading compartment, HLA-DM facilitates the exchange of the CLIP fragment for high-affinity peptides. MHC class II molecules are transported to the plasma membrane, even when peptide loading has failed (middle). Surface MHC class II molecules can be actively removed by the action of the ubiquitin ligase MARCH1, which may cycle between the MHC class II loading compartment and the plasma membrane (left). Residual MARCH1 expression in activated pDCs but not cDCs allows continued presentation of ‘new’ peptide–MHC class II complexes exclusively in activated pDCs.

    It has been more than 100 years since Dr. William B. Coley reported the regression of tumors in some patients who had been injected with bacterial extracts and had developed a high fever. Since this early exercise in cancer vaccination, clinicians and scientists have attempted to harness the immune system to mediate the rejection of tumors in vivo. Because of many important recent discoveries in immunology and tumor cell biology, doctors now have the exciting opportunity to explore and prove the therapeutic potentials of Dendritic Cell vaccines.

    In 2001 since day #1, Dr. Robert Gorter has applied “fever-range, total-body” hyperthermie (fever up to 39° Celsius) in combination with the application of patients’ own dendritc cells prepared by Dr. Gorter in his own laboratory in Germany.

    Dr. Gorter:

    “To the best of my knowledge, there have been published only very positive clinical studies with Dendritic Cells in almost every kind of tumor. But, there were no complete remissions in stage-IV cancer patients (less than 6 months life expectancy).”

    Interestingly, Dr. Gorter and his team could document complete remissions in all cancer groups with stage IV cancer and almost all of them are up to 14 years free of cancer: from 8% in malignant melanoma to 18% in breast- and prostate cancer to 48% in recurrent Glioblastoma multiforme. In 2011, this non-toxic  treatment model (protocol) has been baptized as the Gorter Model in 2011 by a few news paper journalists and television interviewers who both interviewed numerous patients of Dr. Gorter and Dr. Gorter himself.

    Ralph Marvin Steinman (1943-2011)

    Ralph Marvin Steinman (1943-2011) was a Canadian immunologist and cell biologist at Rockefeller University, who in 1973 coined the term dendritic cells while working as a postdoctoral fellow in the laboratory of Zanvil A. Cohn, also at Rockefeller University. Steinman was one of the recipients of the 2011 Nobel Prize in Physiology or Medicine.

    On October 3, 2011, the Nobel Committee for Physiology or Medicine announced that he had received one-half of the Nobel Prize in Physiology or Medicine, for “his discovery of the dendritic cell and its role in adaptive immunity”. The other half went to Bruce Alan Beutler and Jules A. Hoffmann, for “their discoveries concerning the activation of innate immunity”. However, the committee was not aware that he had died three days earlier, on September 30, from pancreatic cancer. This created a complication, since the statutes of the Nobel Foundation stipulate that the prize is not to be awarded posthumously. After deliberation, the committee decided that as the decision to award the prize “was made in good faith”, it would remain unchanged.

    Steinman had received numerous other awards and recognitions for his lifelong work on dendritic cells, such as the Albert Lasker Award For Basic Medical Research (2007), the Gairdner Foundation International Award (2003), and the Cancer Research Institute William B. Coley Award (1998). In addition, he was made a member of Institute of Medicine (U.S.A.; elected 2002) and the National Academy of Sciences (U.S.A.; elected 2001).

    Bruce Alan Beutler (*1957)

    Bruce Alan Beutler (*1957) is an American immunologist and geneticist. Together with Jules A. Hoffmann, he received one-half of the 2011 Nobel Prize in Physiology or Medicine, for “their discoveries concerning the activation of innate immunity” (the other half went to Ralph M. Steinman for “his discovery of the dendritic cell and its role in adaptive immunity”). Beutler is currently Director of the Center for the Genetics of Host Defense at the University of Texas Southwestern Medical Center in Dallas, Texas.

    Jules A. Hoffmann (*1941)

    Jules A. Hoffmann (*1941) is a Luxembourg-born French biologist. During his youth, growing up in Luxembourg, he developed a strong interest in insects under the influence of his father, Jos Hoffmann. This eventually resulted in the younger Hoffmann’s dedication to the field of biology using insects as model organisms. He currently holds a faculty position at the University of Strasbourg. He is a research director and member of the board of administrators of the National Center of Scientific Research (CNRS) in Strasbourg, France. He was elected to the positions of Vice-President (2005-2006) and President (2007-2008) of the French Academy of Sciences. Hoffmann and Bruce Beutler were jointly awarded a half share of the 2011 Nobel Prize in Physiology or Medicine for “their discoveries concerning the activation of innate immunity.”

    Hoffmann and Lemaitre discovered the function of the fruit fly Toll gene in innate immunity. Its mammalian homologs, the Toll-like receptors, were discovered by Beutler. Toll-like receptors identify constituents of other organisms like fungi and bacteria, and trigger an immune response, explaining, for example, how septic shock can be triggered by bacterial remains.

    Why have Dendritic Cell vaccinations and the Gorter Model at large not taken off as a current non-toxic treatment of the oncologic patient?

    Since 2017, there is a body of peer-reviewed literature on the efficacy of Dendritic Cell therapies. After the Nobel Prize for medicine in 2011, all oncologists agree that the root of cancer is always to be found in a suppressed (deficient) immune system. Still, what oncologists currently do is continuing applying chemotherapy and radiation which all have (without exception) significant immunosuppressing effects; and even cause cancer due to their immunosuppressing actions.

    But, here is one answer:

    Dr. Gorter tells:

    “Globally, the business with chemotherapy and radiation is a hundreds-of-billions of Euros (Dollars) industry and a lot of money has been invested and, in return, ten to 25 times more is being earnt. Secondly, pharmaceutical companies and hospitals and doctors alike are making (huge) profits of people who are ill. Hospitals and modern medicine wants you to get or be ill as there would be hardly and health industry left. Therefore, in modern medicine, there is very little money and attention for prevention of illness or non-toxic treatment modalities. Ninety-nine percent of what medical students learn is about disease and standards protocols how to treat with patented medications. Less than 1% is spent on prevention of disease.”

    Eric Hoorn (l), Robert Gorter (m) and Lieneke Hoorn (r) during Eric’s farewell party

    Eric Hoorn (l), Robert Gorter (m) and Lieneke Hoorn (r) during Eric’s farewell party in Alkmaar, the Netherlands, July 3rd, 2014. Eric Hoorn is a patient who followed the Gorter Model at the Medical Center Cologne (MCC) in Germany since 2006 for his rapidly progressing malignant melanoma. Quickly, his generalized metastases disappeared and new metastases did no longer occur. After one year, all his repetitive following scans showed no longer tumor activity, and his routine scans and follow-up visits have been discontinued in 2015. In 2017, Eric is enjoying his life and is the leader of a popular jazz band in The Netherlands


    Resources:

    www.gorter-model.org
    www.cell.com/trends/immunology/fulltext/S1471-4906(16)30140-5
    https://www.ncbi.nlm.nih.gov/pubmed/24872109
    https://www.researchgate.net/…/262697825_Clinical_use_of_dendritic_cells_ for_cancer_therapy