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The Issels Non-Toxic Vaccine Program

The Issels Integrative Immunotherapy program distinguishes itself decisively from the mere administration of a vaccine.

The Vaccine Program at Issels Integrative Oncology Centers™ comprises cutting-edge specific autologous (prepared from the patient's own blood) non-toxic vaccine and cell therapy protocols.

We integrate vaccine and cell therapies that stimulate the body's adaptive and innate immunities into our very comprehensive immunobiologic core treatment which specifically targets the tumor microenvironment to optimize the results.

Recent research findings reveal the crucial role of the tumor microenvironment in the progression or regression of cancer and confirm our clinical experience of 60 years with the Issels Integrative Immunotherapy and its track record of complete long-term cancer remissions.

Watch over 40 videos of patient testimonials

Vaccines - Personalized Targeting of Your Cancer

Physician explaining the Issels cancer vaccine to a patient.• Extracorporeal Photopheresis with the Autologous Dendritic Cell Vaccine

Extracorporeal Photopheresis is a leukapheresis-based immune-modulatory therapy. It is FDA-approved for cutaneous T-cell lymphoma based on research by Richard L. Edelson, Carole L. Berger et al, at Yale University.

During Extracorporeal Photopheresis the blood passes through an ultraviolet light chamber, which has an enormous immune boosting effect. In the cell separator white blood cells, the cells of the immune system such as monocytes and lymphocytes, are separated from the blood which is returned to the body in a closed circuit.

The separated monocytes are cultured outside the body into active dendritic cells. When these potent dendritic cells are re-injected into the body they have the potential to invoke an anti-tumor immune system response. Read more >>

• Autologous Dendritic Cell Vaccine

Dendritic cell vaccine, approved by the US FDA since 2010, is a potent form of immunotherapy to harness the body's own immune system to fight cancer. Dendritic cells are key regulators of the immune responses and orchestrate innate and adoptive immunities. As the most potent antigen presenting immune cells they are responsible for identifying pathogens (viruses, fungi, bacteria, malignant cells) and presenting their identifying markers, antigens, to specific T-lymphocytes that then multiply and attack the disease.

They are also capable of identifying normal dying cells and presenting their antigens to different T-cells that tell the immune system not to attack its own tissues. Read more >>

• Prostate Cancer Vaccine

The Prostate Cancer Vaccine is designed to stimulate a patient's immune system to target prostate cancer cells. The preparation of the vaccine involves culturing the patient's peripheral monocytes in vitro in the presence of a recombinant growth factor, special cytokines and their own prostate-specific antigen, which is fractionated into peptides in order to achieve a more specific immune response. Read more >>

• Coley's Mixed Bacterial Vaccine

Research findings suggest that this vaccine activates the innate immune system, opens blockades in the body's connective tissues, enhances the formation of the body's own interferons, interleukins, colony stimulating factors, tumor necrosis factor, and other potent disease fighters. Read more >>

• Issels' Autologous Vaccine

Issels autologous vaccine is cultured from the patient's own blood that represents his/her own unique internal bodily environment. The preparation follows procedures that favor the development of antigenic peptides and other immunogenic compounds aiming to enhance the body's own cancer fighting mechanisms. Read more >>


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Why They Are Important - Cytokines, Lymphokine-Activated Killer Cells, Natural Killer Cells and Stem Cells

Personalized cancer vaccines.Lymphokine-Activated Killer Cells, also known as LAK Cells, are lymphocytes that in the presence of Interleukin-2 are stimulated to kill cancer cells. Stem cells are the body's master cells that can replace dying or lost cells and aid in the repair of damaged tissue. These protocols are administered at our Integrative Oncology Centers according to individual needs. We invite you to find out more information.

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Immunotherapy for cancer is based on the principle that the host's immune system is capable of generating immune responses against tumor specific antigens. Natural Killer Cells (NKC), in particular, have been shown to eliminate solid tumors and metastatic cells in the circulation through their cytotoxicity and cytokine production.

In 2009, a retrospective analysis of NKC counts included 129 cancer patients who underwent the Issels Treatment® program at the Issels Medical Center in Santa Barbara, California. NKC response to Issels Treatment® protocol revealed an average 48% increase in absolute NKC levels per patient in approximately 3 weeks.

DISCLAIMER: The extent of the response to the vaccines or the overall treatment varies from patient to patient, even with similar diagnosis. Even if the type of the cancer cells is the same, the internal bodily environment on which these cells grow, is unique to each individual patient.


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Additional Information on Our Cancer Vaccines

Extracorporeal Photopheresis with the Autologous Dendritic Cell Vaccine

Dendritic cells (DC) are highly specialized antigen-presenting immune cells and play a key role in the immunological reactions throughout the body. They are responsible for identifying pathogens such as viruses, fungi, bacteria, and malignant cells, by presenting their identifying markers (antigens) to specific T-lymphocytes, which then multiply and attack only the diseased cells, not normal healthy cells.

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.

Dr. Ralph Steinman was awarded the Nobel Prize in Medicine 2011 for his discovery of the dendritic cell and its role in adaptive immunity.

Dr. Harmon Eyre, the Vice President of Research at the American Medical Association commented: “Patients’ responses are far out of proportion to anything that any current therapy could do”.

For over 10 years we have integrated the dendritic cell vaccine into our comprehensive immunobiologic treatment program for all types of lymphomas and solid tumors. Experience has shown that a comprehensive immunobiologic treatment which brings about connective tissue inflammation with its cytokine cascade, can enhance activation, mobilization, and maturation of dendritic cells, and herewith the effectiveness of the vaccines.

We administer the dendritic cell vaccine with or without the extracorporeal photopheresis according to the individual patient's type and stage of the cancer. We always culture the dendritic cell vaccine in the presence of the patient’s tumor antigens in order to potentiate its effectiveness. Doses and interval depend on the patient's response and general condition. The side effects that some patients experience may include flu-like symptoms with a rise of body temperature for several hours and pain or tenderness in the tumor area for several hours or days.

References:

Barr, Joseph. "Clinical Applications of Dendritic Cell Cancer Vaccines”. The Oncologist 4(2): 140-144, 1999.

Berger CL1, Hanlon D, Kanada D, Girardi M, Edelson RL. "Transimmunization, a novel approach for tumor immunotherapy." Transfus Apher Sci. 2002 Jun;26(3):205-16.

Nagaraj S, Ziske C, Schmidt-Wolf IG. "Dendritic cell, the immunotherapeutic cell for cancer." Indian J Med Res. 2004 Apr;119(4):133-8.

O'Neill DW. "Dendritic cells and T cells in immunotherapy." J Drugs Dermatol. 2010 Nov;9(11):1383-92. Review.

Rolinski J, Hus I. "Dendritic-cell tumor vaccines." Transplant Proc. 2010 Oct;42(8):3306-8. Review.

Turnis ME, Rooney CM. "Enhancement of dendritic cells as vaccines for cancer."
Immunotherapy. 2010 Nov;2(6):847-62. Review.

Whiteside TL, Odoux C. "Dendritic cell biology and cancer therapy. " Cancer Immunol Immunother. 2004 Mar;53(3):240-8. Epub 2003 Dec 18.



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Prostate Cancer Vaccine

Hormone-refractory prostate cancer is a disease that is incurable by current standard treatments. Research points to Immunotherapy as a possible recourse in this regard.

For hormone-refractory patients, as well as for prostate cancer patients at any stage, we provide a vaccine which represents an autologous cellular immunotherapy.

It can be classified as an active specific immunotherapy, which is designed to stimulate a patient's immune system to target prostate cancer cells. The preparation of the vaccine involves culturing the patient's peripheral monocytes and dendritic cells in vitro in the presence of a recombinant growth factor, GM-CSF, special cytokines and their own prostate-specific antigen, which is fractionated into peptides in order to achieve an even more specific immune response.

Dendritic cells (DC) are highly specialized antigen-presenting cells and play a key role in the immunological reactions throughout the body.

Doses and interval depend on the patient's response and general condition. The side effects that some patients may experience comprise flu-like symptoms, a rise of body temperature for several hours and pain or tenderness in the tumor area for several days.

References:


Sam S Chang, MD, FACS, Rev. Urol. 2007; 9(Suppl 2): S13–S18. PMCID: PMC1887817. "Treatment Options for Hormone-Refractory Prostate Cancer"

Longo DL (July 2010). "New therapies for castration-resistant prostate cancer". N. Engl. J. Med. 363 (5): 479–81. doi:10.1056/NEJMe1006300. PMID 20818868.


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Coley's Mixed Bacterial Vaccine

Injection of a cancer vaccine.Fever inducing Mixed Bacterial Vaccine treatment has been an integral part of the integrative Issels Treatment® since 1951.

This treatment for cancer was pioneered by William B. Coley, who was the Attending Bone Surgeon at Memorial Hospital, now Memorial Sloan Kettering Cancer Center New York, from 1893 to 1936.

Mixed Bacterial Vaccines (MBV) contain a combination of heat killed bacteria, e.g. gram positive Streptococcus pyogenes and gram negative Bacillus prodigiosus, now called Serratia marcescens. In 1943, M.J. Shears, researcher at the National Cancer Institute, discovered that the biologically active substance in Coley's Mixed Bacterial Vaccine is lipopolysaccharide (LPS) that occurs in the cell walls of gram-negative bacteria.

Administered intramuscularly or intravenously, depending on the individual condition of patients who qualify for this treatment, these vaccines induce fever for several hours. During the rise of the fever, patients get chills and feel flu-like symptoms, such as headache, back pain, nausea and pain in the tumor area. In some cases a drop of blood pressure has been observed. Tumors may swell during the fever treatment and sometimes, a few days after, patients may notice a reduction in tumor size.

Research studies explain the anti-tumor effect of Coley's Mixed Bacterial Vaccine through induction of interferon, augmentation of natural killer cell activity, stimulation of lymphoid tissues, activation of macrophages, induction of serum factor that causes necrosis of tumors, as well as stimulation of interleukin 2.

Fever therapy not only has a significant effect on the immune system but on all the defense zones, and especially the reticulo-histiocytary defense zone and the pluripotent mesenchyme (connective tissues). This is also referred to as the "regulatory ground system" which is the system of basic regulation.

Clinical research suggests that the restoration of basic regulatory mechanisms appears to be an important precondition for specific immunotherapy to reach its optimal effect.

Starting in 1951, in his hospital in Germany, Josef M. Issels, M.D. administered, as one part of his integrative immunotherapy fever treatments without any adverse side effects or complications to thousands of patients suffering from progressive metastatic cancer. He was the only physician systematically applying this treatment to a large patient population. Studies carried out in his hospital comparing the white blood count before and shortly after fever therapy showed the remarkable immune enhancing effect of fever therapy.

References:

Hoption Cann SA, van Netten JP, van Netten C "Dr. William Coley and tumor regression: a place in history or in the future." Postgrad Med J 2003; 79:672-680.

Hoption Cann SA, van Netten JP, van Netten C, Glover DW "Spontaneous Regression: a hidden treasure buried in time." Med Hypotheses 2002; 58 (2):115-9.

Hoption Cann SA, Gunn HD, van Netten JP, van Netten C "Spontaneous Regression of pancreatic cancer." Case Rep Clin Pract Rev 2004; 1.

MacAdam DH, "Spontaneous Regression: Cancer and the Immune System" Chapter two 'Coley', Xlibris:Philadelphia 2003.

Heine H, M.D. "Matrix and Matrix Regulation" Significance of the extracellular matrix. Lecture at Biological Therapy Symposium, 1992, Lisbon, Portugal.

Issels JM, M.D."Cancer: A Second Opinion" 1999, New York, Avery Publ. Group ISBN 0-89529-992-5.


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Issels Autologous Vaccine

Skilled physicians help you to fight your cancer using immunotherapy.Clinical research suggests that the Autologous Vaccine works in a very complex way at the levels of cell-mediated and humoral immunity, and stimulates the formation and activation of T-helper cells. It is cultured from the patient's own blood that represents his/her own unique internal bodily environment. The preparation follows procedures that favor the development of antigenic peptides and other immunogenic compounds aiming to enhance the body's immune functions.

The vaccine is sterile. Since it is custom prepared from the patient's own blood, side effects typically associated with other treatments are not experienced. A slight rise in temperature, fatigue, and tenderness in the tumor area are possible for a period of 6 to 48 hours after administration.

Experience has shown that the effectiveness of the vaccine, or of any vaccine, is enhanced when it is administered within a comprehensive biological treatment program.

Dr. Josef Issels pursued research on immunological and microbiological aspects of cancer etiology since 1948. He established several research departments in his hospital from its inception in 1951. Already in the early years, Dr. Issels and his co-researchers developed cancer vaccines in laboratories located on the premises.

In 1970, the hospital grew from 85 to 120 patient beds and expanded its extensive research facilities into microbiological, immunological, dental departments, and the hyperthermia department, etc.

From 1958 until 1973, Dr. Franz Gerlach was Director of Research of the microbiological department of Dr. Issels' hospital. Dr. Gerlach, was a professor of the University of Vienna, Austria, and represented Austria at the 1946 International Conference of Microbiology of Cancer. He worked at the Pasteur Institute in Paris, was a Fellow of the reputable Academy of Medicine in Paris, among other institutions, and was well known to oncologists all over the world for his research on mycoplasmas and cancer. Dr. Issels' hospital became the only such institution of the era to conduct research on mycoplasmas in cancer and chronic degenerative diseases.

A variety of studies in Dr. Issels' microbiological department confirmed that mycoplasma species can be causative or co-factors in the development of cancer. For example, after cell free depot inoculation of mycoplasmas under the skin of 209 albino mice, 90.9% developed all types of malignancies, whereas of 600 control animals which were not inoculated, only 0.83% developed cancer.

Recent research by reputable scientists such as Drs. S.C. Lo, Chief of Molecular Pathology at the Armed Forces Institute of Pathology in Washington, D.C., S. Tsai, D.J. Wear, J.W. Shih, B. Zhang, R. Dudler, C. Schmidhauser and others, suggests an association between mycoplasmas and malignancy, as well as with AIDS.

Drs. M. Nasralla, J. Haier, G.L. Nicolson, professor at M.D. Anderson Cancer Center, Houston, Texas, and the Institute for Molecular Medicine, Huntington Beach, California, et al. confirm the involvement of certain mycoplasma species in the Gulf War Syndrome, Chronic Fatigue Syndrome, Fibromyalgia, and Rheumatoid Arthritis.

For more than a century, international researchers have precisely documented certain microorganisms in human blood, body fluids and tissues, which were highly "pleomorphic", i.e. they can appear in various developmental stages and in diverse forms while maintaining their essential characteristics.

When the host terrain deteriorates, they have been observed to transform from primitive structures into higher cyclogenetic structures. They can become pathogenic and may be causative or contributory factors in the development of malignancies, various chronic degenerative diseases and immune disorders. Some researchers have observed that disease causing higher cyclogenetic structures can be reversed by the administration of lower cyclogenetic structures.

Different scientists have given different names to these microorganism. However, they all have documented essential features in common: the microbes are stainable, cell wall deficient, virus-like and pleomorphic. They are classified as stealth pathogens.

References:

Gerlach F
Zur Biologie der Mykoplasmen und ueber ihre Beziehungen zu malignen Tumoren" Wiener Tieraerztliche Monatsschrift, 1970, No.6/7, 232-245.

Gerlach F
"Participation of Mycoplasmas in Oncogenesis" 1975, Wiener Medizinische Wochenschrift No. 4, Suppl.26.

Issels JM
"Immunotherapy in Progressive Metastatic Cancer A Fifteen-Year Survival Follow-up" 1970, Clinical Trials Journal 7(3): 357-366, London.

Issels JM
"Cancer: A Second Opinion" 1999, Avery Publishing Group, New York.

Tsai S, Wear DJ, Shi W, Lo SC
"Mycoplasmas and oncogenesis: persistent infection and multistage malignant transformation "1995, Proc. Natl. Acad. Sci. USA; 92(22):10197-201.


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Additional Information on Our Cancer Vaccine Programs

The extensive Issels experience with Immunotherapy has shown that the integration of Vaccine and Cell Therapies into our comprehensive immunobiologic core treatment program achieves better outcomes than their administration alone.

The Vaccine and Cell Therapies stimulate the body’s adaptive and innate immunities, whereas the comprehensive core treatment program targets also the tumor microenvironment with its crucial role in defense. The synergistic effect of the various modalities of Integrative Immunotherapy improves treatment results.

References:

Sounni NE, Noel A. Targeting the tumor microenvironment for cancer therapy.
Clin Chem. 2013 Jan;59(1):85-93. doi: 10.1373/clinchem.2012.185363. Epub 2012 Nov 28.

BACKGROUND:
With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic.

CONTENT:
The malignant features of cancer cells cannot be manifested without an important interplay between cancer cells and their local environment. The tumor infiltrate composed of immune cells, angiogenic vascular cells, lymphatic endothelial cells, and cancer-associated fibroblastic cells contributes actively to cancer progression. The ability to change these surroundings is an important property by which tumor cells are able to acquire some of the hallmark functions necessary for tumor growth and metastatic dissemination. Thus in the clinical setting the targeting of the tumor microenvironment to encapsulate or destroy cancer cells in their local environment has become mandatory. The variety of stromal cells, the complexity of the molecular components of the tumor stroma, and the similarity with normal tissue present huge challenges for therapies targeting the tumor microenvironment. These issues and their interplay are addressed in this review. After a decade of intensive clinical trials targeting cellular components of the tumor microenvironment, more recent investigations have shed light on the important role in cancer progression played by the noncellular stromal compartment composed of the extracellular matrix.

SUMMARY:
A better understanding of how the tumor environment affects cancer progression should provide new targets for the isolation and destruction of cancer cells via interference with the complex crosstalk established between cancer cells, host cells, and their surrounding extracellular matrix.

Emens LA, Silverstein SC, Khleif S, Marincola FM, Galon J.
"Toward integrative cancer immunotherapy: targeting the tumor microenvironment."
J Transl Med. 2012 Apr 10;10:70. doi: 10.1186/1479-5876-10-70.

Leibovici J, Itzhaki O, Huszar M, Sinai J.
The tumor microenvironment: part 1.
Immunotherapy. 2011 Nov;3(11):1367-84. doi: 10.2217/imt.11.111. Review.

Leibovici J, Itzhaki O, Huszar M, Sinai J.
Targeting the tumor microenvironment by immunotherapy: part 2.
Immunotherapy. 2011 Nov;3(11):1385-408. doi: 10.2217/imt.11.112. Review. PMID

Sounni NE, Noel A.
Targeting the tumor microenvironment for cancer therapy.
Clin Chem. 2013 Jan;59(1):85-93. doi: 10.1373/clinchem.2012.185363. Epub 2012 Nov 28.

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Last updated: 9/15/2014
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