Article by Dr. Richard Fuller - DOVE CLINIC

Immunotherapy Treatments for Cancer

by Dr Richard Fuller

published in Positive Health issue 172 - July 2010

When we think about our immune system we usually consider its importance in fighting colds and flu, yet significant evidence highlights its key role in preventing and treating cancer.

Remarkable cases have been published of people with advanced tumours undergoing spontaneous complete remission against all the odds, sometimes following fever or infection (Bodurtha, 2006). Such cases provide a glimpse of the extraordinary power of our immune system to fight cancer.

This article aims to review one of the most exciting and important modern medical questions how can we harness this power of our immune system to prevent or destroy cancer?

First we need to explore if there is convincing evidence that our immune system has such a capacity against cancer, and then we can review nutritional and innovative treatments which are being researched to optimize our response.

Introduction

Between 1975 and 2004, cancer rates increased in the UK by 25%. At current levels, one in three people develop cancer during their lives. The mainstay of conventional treatment remains surgery where possible, radiotherapy to prevent or palliate local recurrence of the tumour, and chemotherapy for widespread or advanced cancer.

There are many examples of success with this approach, and for many cancers conventional management is highly effective. Yet published reviews have reported that chemotherapy adds just 2.3% to overall 5 year cancer survival (Morgan, 2004).

Many tumours remain resistant to chemotherapy approaches, which are currently non-selective, meaning they affect healthy multiplying cells as well as cancer. This causes frequent side effects and immune suppression.

It seems appropriate to look at further treatment approaches that act in a different and less toxic way, adding to the fight against cancer. The immune system is highly complex and there are many puzzles yet to be solved, but evidence suggests working in collaboration with our immune system has great potential. This is the field of cancer immunotherapy.

Is Immune Function Important in Preventing Cancer?

Yes! Let's look at some of the evidence. A large study published in The Lancet followed over 3,600 healthy people in Japan for 11 years. They found those with poor cell-mediated immune function had significantly higher rates of a variety of cancers and infections compared to those who had good immune function (Matsayuma, 2000).

Another way to look at this takes people who are known to have very poor immune function, such as people who take immunosuppressive medication following organ transplant. For such patients these drugs are essential to prevent a rejection of the donor organ; yet cancer rates in these people have been reported to be 7.1 times higher than the general population (Dantal et al.2005). Other medical conditions such as HIV which cause specific immune deficiency are also associated with higher rates of a variety of cancers.

This process of immune protection to cancer has been coined 'immunosurveillance', with immune cells such as Natural Killer Cells and Dendritic Cells in a state of constant monitoring through our bodies, finding and targeting cancer cells and breaking them down long before they become evident.

So, are we developing problems with our immune function leading to increased rates of illness? There are various theories under study looking to see if immune function in our population is changing, leading to increased rates of asthma and eczema, autoimmune disease and life threatening illness.

These theories include the hygiene-hypothesis which states exposure to some infections may support healthy immune function and may actually be protective against cancer. Also, stress-related changes reduce our cell-mediated immune function (Glasser et al. 2001) as well as micronutrient deficiency due to our consumption of refined 'empty' calories and nutrient depleted foods (Gallagher-Allred et al '96, Bistrian et al '76, Naber et al '97). All of these factors may be contributing to a detrimental shift in our immune system.

One thing is for certain in modern society as we get older we undergo a decline in our immune function. This process has been termed 'immunosenscence' and is thought to be due to changes within the thymus gland and reduced numbers of T cells ready to respond to challenges (Aspinall 2000). This decline maps the increasing rates of cancer as we age.

Animal cancer studies have even shown that young mice do better with cancer treatments than older mice (Liu, 2008). So, should we look at ways to support immune function in people undergoing cancer treatment or aiming to stay cancer free?

Improving Immune Function Supplementation?

We know the essential basics: eat fresh fruit and vegetables, reduce stress and make sure you get your sleep. What else can we do? Here are two supplements with a good evidence base.

Immiflex contains 1-3, 1-6 beta glucan together with Vitamin D3. Firstly, many people in UK are deficient in Vitamin D, which has a wealth of recent research highlighting its importance in immune function. The beta glucan in Immiflex is refined from the cell wall of baker's yeast and has an excellent safety profile.

It has undergone many studies showing impressive ability to improve the activity of our main frontline immune cells called neutrophils, resulting in reduced viral and post operative infection. It has also been researched alongside 'monoclonal antibodies' which are a conventional form of cancer immunotherapy. These antibodies have the ability to target certain proteins or markers associated with cancer. The monoclonal antibodies kill cancer cells by marking them so other immune cells pick them out. Extremely promising animal studies show an ability to improve cancer outcomes when monoclonal antibodies and beta glucan are given together.

This is now being followed up by international trials on cancer patients.

AHCC (Active Hexose Correlated Compound) is another functional food supplement derived from Basidiomycetes mushrooms. Research indicates significant improvement in Natural Killer cell activity as well as evidence from Yale Medical School demonstrating improved T-cell activity in older people, thereby helping to improve markers of age-related immune decline (Matsui et al 2002). Some studies have also reported extended survival of cancer patients using AHCC alongside other treatment.

In addition to these targeted supplements for immune function, there have been published reports that multivitamins; Vitamin C, E, selenium and zinc can be of benefit in improving immune function in older people who are often at risk of low nutrient intake (Mitchel et al, 2003).

Immunotherapy Approaches to Cancer

Dr William Coley pioneered the immunotherapy vaccine approach in 1891 after witnessing a patient with a type of bone cancer become cancer-free following a severe skin infection. He developed a method of injecting mixtures of killed bacteria into his cancer patients, and during his career reported many excellent outcomes.

Over 100 years later and the vaccine approach has been highly researched and developed with the aim of triggering an immune response against cancer. Modern techniques include using viruses which are not harmful to healthy cells but are capable of killing or labelling cancer cells for the rest of the immune system (oncolytic viruses), the use of harmless bacteria such as Mycobacterium vaccae which have an effect to modulate immune function, and even modifying T cells specifically to recognize surface markers taken from the tumour sample.

Results are encouraging, and at this stage research is ongoing to discover why some people dramatically improve and others don't respond (Wolf et al, 2003). A major benefit of this approach is that side effects are typically restricted to fever and short-lived flu-like symptoms.

Dendritic Cell Vaccination

There is much exciting research in the field of cancer vaccines (Rosenberg, 2004). One particularly promising approach uses dendritic cells which are created from the patient's own blood cells called monocytes. Dendritic cells are the natural scouts within our body. They provide feedback to our immune system, orchestrating which cells to kill and which to ignore.

It's possible to produce many dendritic cells and expose them to samples of the patient's own tumour, or similar markers from laboratory samples. These primed dendritic cells can then be given back to the patient in an attempt to establish an immune response against the cancer. Recently, a vaccine which contains the patient's own dendritic cells primed for antigen markers found on prostate cells has been given FDA approval for the treatment of prostate cancer.

Further new cancer treatments such as Photodynamic Therapy have been shown to break down cancer cells in a way which is more visible to the immune system than cell death due to chemotherapy (Korbelik et al). Potentially, these new approaches can be combined with other forms of immunotherapy to increase the anti-tumour immune response.

Summary

The immune system is one of the finest masterpieces of the human body and needs to be provided the right nutrients and environment to work effectively. By combining conventional medicine and nutrition with an understanding of the importance of the immune system, there is the potential to prevent and treat many health problems including cancer.

References and Further Reading

Prestwich F Errington P and Hatfieldy. The Immune System is it Relevant to Cancer Development, Progression and Treatment? Clinical Oncology 20: 101. 2008.

Bodurtha et al. A clinical, histologic, and immunologic study of a case of metastatic malignant melanoma undergoing spontaneous remission. Vol 37.2, 735 742. 2006.

Morgan et al. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clinical Oncology: 16 ( 8): 549-560. December 2004.

Glasser et al Evidence for a Shift in the Th-1 to Th-2 Cytokine Response Associated With Chronic Stress and Aging. Journal of Gerontology. 56A 2001.

Aspinall R and Andrew D. Imunosenescence: potential causes and strategies for reversal. Biochem Soc Trans 28(2): 250-4. Feb 2000.

Liu et al. Overcoming immune evasion in T cell therapy of cancer: lessons from animal models. Curr Mol Med 8(1): 68-75. Feb 2008.

Matsui Y, et al. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. J Hepatol 37:78-86. 2002.

Dantal et al. Immunosuppressive Drugs and the Risk of Cancer after Organ Transplantation. New England Journal of Medicine..352: 1371-1373. 2005.

Korbelik M. Induction of tumor immunity by photodynamic therapy. J Clin Laser Med Surg 14:329-334. 1996.

Driscoll M, Hansen R, Ding C, Cramer D and Yan J. Therapeutic potential of various -glucan sources in conjunction with anti-tumor monoclonal antibody in cancer therapy. Cancer Biology & Therapy 8 (3): 216-223; 1 February 2009.

Hong F, Yan J, Baran JT, Allendorf DJ, Hansen RD, Ostroff G, Xing, PX, Cheung NV and Ross G D. Mechanism by Which Orally Administered -1,3-Glucans Enhance the Tumorcidial Activity of AntiTumor Monoclonal Antibodies in Murine Tumor Models. J. Immunol. 173:797-806. 2004.

Cramer DE, Allendorf DJ, Baran JT, Hansen RD, Marroquin J, Li B, Ratajczak J, Ratajczak MZ, and Yan J. Beta-Glucan Enhances Complemented-Mediated Hematopoietic Recovery After Bone Marrow Injury. Blood 107 (2). 2006.

Yan, J, Vetvicka V, Xia Y, Coxon A, Carroll MC, Mayadas TN and Ross GD. -Glucan, a 'specific' biologic response modifier that uses antibodies to target tumors for recognition by complement receptor 3 (CD11b/CD18). J. Immunol 163: 3045-52. 1999.

Dellinger EP, Babineau TJ, Bleicher P, Kaiser AB, Seibert GB, Postier RG, Vogel SB, Norman J, Kaufman D, Galandiuk S and Condon RE. Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group. Arch Surg.134(9): 977-83. Sep 1999.

Matsui Y et al. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a cohort study. J Hepatol. 37(1): 78-86. Jul 2002.

Mitchel et al. Supplementation with vitamins or minerals and immune function: can the elderly benefit? Nutrition Research, Volume 23 (8): 1117-39. 2003.

Hong F, Hansen R, Yan J et al. Glucan Functions as an Adjuvant for Monoclonal Antibody Immunotherapy by Recruiting Tumoricidal Granulocytes as Killer Cells. Cancer Research. 63: 9023-9031. December 15 2003.

Castano AP, Mroz P and Hamblin MR. Photodynamic thera py and antitumor immunity. Nat Rev Cancer 6:535-545. 2006. Rosenberg et al. Cancer immunotherapy: moving beyond current vaccines. Nature Medicine 10: 909 15. 2004.

Wolf A, Wolf D, Steurer M and Guenther G. Increase of Regulatory T Cells in the Peripheral Blood of Cancer Patients. Clinical Cancer Research 606 (9): 606-12. 2003.

Ghiringhelli F et al. CD4, CD25 regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 34: 336-44. 2004.

Kenyon J, Fuller R, Lewis T. Activated Cancer Therapy Using Light and Ultrasound A Case Series of Sonodynamic Photodynamic Therapy in 115 Patients over a 4 Year Period. Current Drug Research. 4 (3). Sept 2009.

Ana P Castano et al. Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model. Proceedings of the National Academy of Science. 105(14): 5495-5500. 2008.

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