Researchers have shown that fresh and vital dendritic cells can be introduced into the body in the form of a vaccine. If cancer is present, inoculation with new dendritic cells alerts the immune system to the presence of cancer and restarts proper immune function. This serves to mobilize the exceptional power of the immune system to identify cancer and combat it. These dendritic cells are cultured from the patient’s own white blood cells (so they are described as “autologous”). Initially, after a simple blood draw, the blood is sent to a high-tech medical laboratory where specially trained cell biologists and technicians separate out certain white blood cells (monocytes) from the blood. These cells are then cultured and transformed in seven days into a new generation dendritic cells. This new generation of vital, activated dendritic cells is re-introduced into the patient’s body through simple intractaneous injections as shown above. The results are remarkable by any standard, increasing immune response, patient survival, and quality of life.
Dendritic cell therapy is now widely recognized as safe [ ] and nontoxic [iii ]with minimal toxicity, at the lowest level—Grade 1. This nontoxic treatment is appropriate for probably all cancer patients and all immune-compromised patients. The injections are generally well tolerated [iv v ] with almost no side effectsexcept for a fever that typically starts the day of the injection and lasts 4 to 24 hours. Temporary side effects documented by Japanese researchers “were low grade fever (78%), chills (83%), fatigue (23%), and some nausea (17%) experienced on the day of the cell [injections].”[vii] Researchers have also pointed out that dendritic cell therapy offers a safe, effective, non-toxic treatment option for children. [ , ] Preliminary studies show that the vaccines are even more effective in younger patients [xi xii] and in early stage cancers.
When we vaccinate for diseases such as tetanus or measles, the injection must be repeated five to six times at defined intervals, in order to establish life-long immunity. Vaccination improves specific immune function, but the immune system must be “trained” through repeated exposures. To improve immune function using dendritic cells, these new cells must be injected at least six times. Patients with all forms of cancer and also patients with chronic viral infections, such as Hepatitis B and C or HIV, are initially vaccinated with dendritic cells six times at monthly intervals. Thereafter, the injections are repeated once every six months for the duration of three years as “booster shots” and then at usually yearly intervals. This ongoing dendritic cell vaccination is another aspect of treatment. Providing the vaccine on a schedule comparable to other vaccine protocols has resulted in an encouraging success rate of effective treatment. The importance of frequent vaccination in the initial stage of treatment has now been validated in scores of recent research studies.
All healthy individuals continuously produce cancer cells throughout their lives. These cells occur on an ongoing basis and because they develop from within the body, they are referred to as autologous. Malignant cells result from the effects of mutations and viruses, and exposure to carcinogens ranging from radiation or, tobacco smoke, to pesticides, and food colorings and preservatives, just to mention a few. It is the primary task of the cellular immune system to detect these cancer cells early and destroy them. It should be understood that in any human being, cancer cells develop by the thousands every day. As long as the immune system can detect early, and contain the flow of newly emerging cancer cells, one can go through life without ever developing clinical cancer. Systemic immunodeficiency is observed in patients with advanced malignant disease.[ ] When cancer occurs, by definition the immune response is suppressed, or there has been an excessive exposure to a carcinogen. Impaired immune function often involves a drop in the number and/or the function of immune cells available to effectively detect or kill cancer cells.Dendritic cells are one of the keys to an effective immune response to cancerous cells. The dendritic cells migrate throughout the tissues of the body, checking for abnormal cells. Dendritic cells also target cells with the potential to become malignant, due to chronic infection by a virus (for example a chronic viral infection in the cervix such as human papilloma virus (HPV) which can develop into a malignancy). When an abnormal cell, such as a cancer cell, has been detected the dendritic cell travels to a nearby lymph node and presents the “ID” (the specific antigen profile) of the cancer cell to be destroyed. If the immune system is no longer able to recognize cancer cells, it cannot destroy malignant cells as they develop day to day. When that occurs, cancer can gain a foothold and grow unchecked. Tumor cells, which may remain undetected for years, are referred to as subclinical cancer. Over time, tumors can continue to develop without detection and amass.
To date 48% of all patients with Glioblastoma multiforme Stage IV went in complete and long-lasting remission. This is remarkable, given that statistics from the medical literature indicate that with standard treatment, about 72% of all patients who have been diagnosed with Glioblastoma multiforme Stage IV die within the first year of diagnosis and only 1% survive three years. These outcomes reflect the positive survival rates frequently seen in the patients at the Medical Center Cologne. Dendritic cell therapy has been an integral aspect of Dr. Gorter’s treatment for more than 10 years. This work has pioneered a very moderate approach to hyperthermia and immunotherapy, developing safe, effective protocols that are now being validated in the peer-reviewed medical literature. Today, research centers worldwide are studying dendritic cell therapy, which continues to emerge “as a potentially powerful, non-toxic and broadly useful vaccination strategy for cancer patients.”
More than 250 research studies have confirmed the effectiveness of this approach to immunotherapy in cancer treatment. Study after study has shown that dendritic cell therapy provides “a significant prolongation in survival.”[i] American studies ofdendritic cell therapy[ have been conducted at major universities including Harvard Medical School, Stanford, UCSF Medical School, University of Maryland, University of Michigan, and University of Texas. In May 2010, the FDA hasapproved dendritic cell therapy[ in patients with metastatic prostate cancer. [ There is broad agreement that dendritic cell therapy [increases the number of T-cells in the body, which results in a stronger immune response[i vi xiii] Italian researchers reported, “Dendritic cell targeting has recently been shown to confer strong and protective cytotoxic T cell-based immunity.”[ ] Studies at research centers around the world have documented the benefits of dendritic cell therapy for many forms of cancer including brain tumors,[ix ]eukemia,[ix ] lymphoma,[xiii ] melanoma,[vi xiii] and a range of other malignancies including cancers of the breast,[xviii] gastrointestinal tract,[vi xiii] liver,[v] lungs,[vii ]pancreas,kidneys,[i xvii] and thyroid.[iv] In the U.S., a controlled phase II study of metastatic prostate cancer conducted in 2009 documented the effectiveness ofdendritic cell vaccinations for prostate cancer [xiv] The most recent studies have found that dendritic cell vaccine significantly prolong patient survival. For example, a recent French study involving 56 cancer patients reported patient survival averaging almost 4 years.[xv] In a Chilean study of 50 patients, those with Stage III cancer survived an average of 4 years. Among those with Stage IV cancer, 60% responded positively to the therapy and lived almost 3 years.[xvi] This is an exceptionally positive result, since life expectancy of Stage 4 patients is usually measured in weeks or months. Each of these studies involved some form of dendritic cell vaccine. A Danish study found that dendritic cell inoculation can double the number of T cells and NK cells in the body in as little as 4 weeks following the injection.[xviii] According to British researchers at the U.K. Institute for Cancer Studies, “Dendritic cells are the most potent of all antigen-presenting cells, with the capacity to take up, process, and present tumor antigens to T cells and stimulate an immune response, thus providing a rational platform for vaccine development. ”[v] Japanese researchers conclude, “Dendritic cells loaded with tumor antigens have been emerging as a new strategy in cancer treatment.”[vi] At the Medical Center Cologne, patients with Glioblastoma multiforme, 48% experience complete, long-lasting remission and another 24% experience a prolonged period of partial remission or stable disease. This is remarkable in the context of the 5% one-year survival rate reported in the medical literature for the average patient diagnosed with stage IV brain tumors die within the first year of diagnosis, although some patients, chemotherapy (Temodal) and radiation experience an additional 6 months life expectancy.[ ] In patients with Stage IV breast cancer, approximately 26% to 28% still go intocomplete and sustained remission, and another approximately 48% experiencepartial remission with improved quality of life and significantly prolonged life expectancy. This nontoxic immune therapy offers an important option in cancer treatment. Dendritic cell vaccines provide another form of treatment for conditions that cannot be addressed with standard chemotherapy or radiation, such as metastatic renal canceri or melanoma. [xiv] The dendritic cell vaccine can be a life-prolonging therapy for Stage III and IV patients and for the vast majority of patients enhances quality of life significantly.
Gilboa E, Nair SK, Lyerly HK. Immunotherapy of cancer with dendritic-cell-based vaccines. Cancer Immunol Immunother 1998;46:82–7. Mashino K, Sadanaga N, Tanaka F, Ohta M, Yamaguchi H, Mori M. Effective strategy of dendritic cell-based immunotherapy for advanced tumor-bearing hosts: the critical role of Th1-dominant immunity. Mol Cancer Ther. 2002 Aug;1(10):785-94. Lemoine FM, Cherai M, Giverne C, Dimitri D, Rosenzwajg M, Trebeden-Negre H, Chaput N, Barrou B, Thioun N, Gattegnio B, Selles F, Six A, Azar N, Lotz JP, Buzyn A, Sibony M, Delcourt A, Boyer O, Herson S, Klatzmann D, Lacave R. Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer. Int J Oncol. 2009 Sep;35(3):569-81. Bachleitner-Hofmann T, Friedl J, Hassler M, Hayden H, Dubsky P, Sachet M, Rieder E, Pfragner R, Brostjan C, Riss S, Niederle B, Gnant M, Stift A. Pilot trial of autologous dendritic cells loaded with tumor lysate(s) from allogeneic tumor cell lines in patients with metastatic medullary thyroid carcinoma. Oncol Rep. 2009 Jun;21(6):1585-92. Palmer DH, Midgley RS, Mirza N, Torr EE, Ahmed F, Steele JC, Steven NM, Kerr DJ, Young LS, Adams DH.A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology. 2009 Jan;49(1):124-32. Tanaka F, Haraguchi N, Isikawa K, Inoue H, Mori M. Potential role of dendritic cell vaccination with MAGE peptides i n gastrointestinal carcinomas. Oncol Rep. 2008 Nov;20(5):1111-6. Kimura H, Iizasa T, Ishikawa A, Shingyouji M, Yoshino M, Kimura M, Inada Y, Matsubayashi K. Prospective phase II study of post-surgical adjuvant chemo-immunotherapy using autologous dendritic cells and activated killer cells from tissue culture of tumor-draining lymph nodes in primary lung cancer patients. Anticancer Res. 2008 Mar-Apr;28(2B):1229-38. Redman BG, Chang AE, Whitfield J, Esper P, Jiang G, Braun T, Roessler B, Mulé JJ. Phase Ib trial assessing autologous, tumor-pulsed dendritic cells as a vaccine administered with or without IL-2 in patients with metastatic melanoma. J Immunother. 2008 Jul-Aug;31(6):591-8.
Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68. Kim JH, Lee Y, Bae YS, Kim WS, Kim K, Im HY, Kang WK, Park K, Choi HY, Lee HM, Baek SY, Lee H, Doh H, Kim BM, Kim CY, Jeon C, Jung CW. Phase I/II study of immunotherapy using autologous tumor lysate-pulsed dendritic cells in patients with metastatic renal cell carcinoma. Clin Immunol. 2007 Dec;125(3):257-67. Epub 2007 Oct 3. Dohnal AM, Witt V, Hügel H, Holter W, Gadner H, Felzmann T. Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy. 2007;9(8):755-70. Epub 2007 Oct 4. De Vleeschouwer S, Fieuws S, Rutkowski S, Van Calenbergh F, Van Loon J, Goffin J, Sciot R, Wilms G, Demaerel P, Warmuth-Metz M, Soerensen N, Wolff JE, Wagner S, Kaempgen E, Van Gool SW. Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme. Clin Cancer Res. 2008 May 15;14(10):3098-104. Molenkamp BG, Sluijter BJ, van Leeuwen PA, Santegoets SJ, Meijer S, Wijnands PG, Haanen JB, van den Eertwegh AJ, Scheper RJ, de Gruijl TD. Local administration of PF-3512676 CpG-B instigates tumor-specific CD8+ T-cell reactivity in melanoma patients. Clin Cancer Res. 2008 Jul 15;14(14):4532-42. Kouiavskaia DV, Berard CA, Datena E, Hussain A, Dawson N, Klyushnenkova EN, Alexander RB. Vaccination with agonist peptide PSA: 154-163 (155L) derived from prostate specific antigen induced CD8 T-cell response to the native peptide PSA… a phase 2 study in patients with recurrent prostate cancer. J Immunother. 2009 Jul-Aug;32(6):655-66. Ménard C, Blay JY, Borg C, Michiels S, Ghiringhelli F, Robert C, Nonn C, Chaput N, Taieb J, Delahaye NF, Flament C, Emile JF, Le Cesne A, Zitvogel L. Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients. Cancer Res. 2009 Apr 15;69(8):3563-9. Epub 2009 Apr 7. López MN, Pereda C, Segal G, Munoz L, Aguilera R, González FE, Escobar A, Ginesta A, Reyes D, González R, Mendoza-Naranjo A, Larrondo M, Compán A,
Ferrada C, Salazar-Onfray F. Prolonged survival of dendritic cell-vaccinated melanoma patients correlates with tumor-specific delayed type IV hypersensitivity response and reduction of tumor growth factor beta-expressing T cells. J Clin Oncol. 2009 Feb 20;27(6):945-52. Epub 2009 Jan 12. Berntsen A, Trepiakas R, Wenandy L, Geertsen PF, thor Straten P, Andersen MH, Pedersen AE, Claesson MH, Lorentzen T, Johansen JS, Svane IM. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial. J Immunother. 2008 Oct;31(8):771-80. Svane IM, Pedersen AE, Nikolajsen K, Zocca MB. Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2. Vaccine. 2008 Aug 26;26(36):4716-24. Epub 2008 Jul 9. Fontana R, Bregni M, Cipponi A, Raccosta L, Rainelli C, Maggioni D, Lunghi F, Ciceri F, Mukenge S, Doglioni C, Colau D, Coulie PG, Bordignon C, Traversari C, Russo V. Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients. Blood. 2009 Feb 19;113(8):1651-60. Epub 2008 Dec 12. Leplina OY, Stupak VV, Kozlov YP, Pendyurin IV, Nikonov SD, Tikhonova MA, Sycheva NV, Ostanin AA, Chernykh ER.Use of interferon-alpha-induced dendritic cells in the therapy of patients with malignant brain gliomas. Bull Exp Biol Med. 2007 Apr;143(4):528-34. Hus I, Schmitt M, Tabarkiewicz J, Radej S, Wojas K, Bojarska-Junak A, Schmitt A, Giannopoulos K, Dmoszyńska A, Roliński J.Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response. Leukemia. 2008 May;22(5):1007-17. Epub 2008 Mar 6. Di Nicola M, Zappasodi R, Carlo-Stella C, Mortarini R, Pupa SM, Magni M, Devizzi L, Matteucci P, Baldassari P, Ravagnani F, Cabras A, Anichini A, Gianni AM. Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease: a pilot study. Blood. 2009 Jan 1;113(1):18-27. Epub 2008 Sep 22.
Hirooka Y, Itoh A, Kawashima H, Hara K, Nonogaki K, Kasugai T, Ohno E, Ishikawa T, Matsubara H, Ishigami M, Katano Y, Ohmiya N, Niwa Y, Yamamoto K, Kaneko T, Nieda M, Yokokawa K, Goto H. A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer. Pancreas. 2009 Apr;38(3):e69-74. Avigan DE, Vasir B, George DJ, Oh WK, Atkins MB, McDermott DF, Kantoff PW, Figlin RA, Vasconcelles MJ, Xu Y, Kufe D, Bukowski RM. Phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma. J Immunother. 2007 Oct;30(7):749-61. Papewalis C, Jacobs B, Wuttke M, Ullrich E, Baehring T, Fenk R, Willenberg HS, Schinner S, Cohnen M, Seissler J, Zacharowski K, Scherbaum WA, Schott M. IFN-alpha skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo. J Immunol. 2008 Feb 1;180(3):1462-70. Gorter R. Unpublished data. Medical Center Cologne, Cologne, Germany. 2010.
Please feel free to contact us to determine if the Gorter Model can also put you on the path of extending your life expectancy and improving the quality of your life!