In past issues of CancerWire we have explored the divide that exists between holistic approaches and conventional cytoxic (cell-killing) therapies when it comes to the treatment of cancer. In general, orthodox medicine believes that a cancer must be poisoned or cut out because the body is incapable of managing or eliminating the disease without outside intervention. In contrast, holistic approaches believe that the body is the best defense against cancer and steps should be taken to strengthen the body’s own innate abilities to control this disease. The orthodox world of providing external interventions and the holistic world of facilitating internal defenses share common ground on the subject of immune therapy.
The Immune System
For decades, mainstream science has held the position that the immune system has little to do with cancer. However, as advances were made in our understanding of the immune system, science realized that this system could affect cancer and that there were various biological mechanisms in place to recognize and eliminate malignant tumors in vivo.
The immune system is an exceedingly complex organization of organs, highly specialized cells, and a circulatory system separate from blood vessels (the lymph system) which work together to clear infections from the body. (1)
The two major types of lymphocytes are B cells, which grow to maturity in the bone marrow, and T cells, which mature in the thymus, located behind the breastbone. B cells produce antibodies that circulate in the blood and lymph and attach to foreign antigens marking them for destruction by other immune cells. B cells are part of what is known as antibody-mediated or “humoral immunity” because the antibodies circulate in blood and lymph which the Greeks called the body’s “humors.” T lymphocytes are responsible for cell-mediated immunity (or cellular immunity). Certain T cells, which also patrol the blood and lymph for foreign invaders, do more than mark the antigens – they can also attack and destroy diseased cells they recognize as foreign. T cells also orchestrate, regulate and coordinate the overall immune response. T cells depend on unique cell surface molecules called the major histocompatibility complex (MHC) to help them recognize antigen fragments. There is much more to the immune system, but here we will turn our focus to cancer.
Immune System and Cancer
It is now known that the immune system not only works to rid the body of infectious organisms like bacteria and viruses, but also plays an important role in cancer. The immune system uses a process known as ‘immunosurveillance’ to help prevent the outgrowth of tumors. Today, researchers believe that this system can be manipulated through “immune therapy” (or “immunotherapy”) to cure or reduce tumor burden in cancer patients. To achieve this goal, several approaches are being tested, including:
• Natural Killer (NK) cells are a type of lethal lymphocyte. They are called “natural” killers because they, unlike cytotoxic T cells, do not need to recognize a specific antigen before they act. They target tumor cells and protect against a wide variety of infectious microbes.
• The use of highly potent antigen-presenting cells called dendritic cells (DCs), which can efficiently activate T cells.
• Using cytokines, such as tumor necrosis factor (TNF) alpha, interferon (IFN) alpha, IFN-beta, interleukin-4 (IL-4), and IL-6, to interact directly with tumor cells, inducing the latter to either commit suicide or stop further growth.
• Using monoclonal antibodies (MAbs) (pure populations of immune system proteins) to attack specific molecular targets. Like a guided missile, monoclonal antibodies can be tipped with poisons or radioactive isotopes to hone in on tumor cells and deliver their payloads.
• In adoptive transfer, researchers isolate antigen-specific T cells from a cancer patient, expand them to large numbers in a test-tube, and re-infuse them back into the patient to kill off the remaining tumor cells.
• Various vaccines such as cell-based, virus-based, and protein and peptide based use the principal of active immunization so the body can better recognize and target the cancer.
Because these innovative approaches are designed to target tumor cells they hold the promise to be substantially less toxic than current therapies like chemo and radiation that indiscriminately kill cells.
To date there has been some success with these approaches. For example, two antibodies have been approved by the FDA for use in cancer treatment. Rituxan is specific for an antigen called CD20, which can be found on the surface of both normal and malignant B-lymphocytes. In a phase III clinical study, 50 percent of patients with non-Hodgkin’s lymphoma (NHL) responded to Rituxan. Herceptin is the other FDA-approved antibody and it is specific for the human epidermal growth factor receptor 2 (HER2) protein. HER2 is over-expressed in 25-30 percent of primary breast cancers and it has been shown to be effective against this disease in phase III clinical studies.
Despite these successes, immunotherapy still has far to go before it provides durable cures for most solid advanced cancers. Both host and tumor related mechanisms can lead to a failure to mount a proper anti-tumor-specific immune response, and these are frequently key factors in limiting the success of cancer immunotherapy.(2)
Plants and the Immune System
Throughout millennia, human cultures have used various naturally occurring plant-based products to help fight infections. In this way, plants have been used to reach the same larger goal that is currently challenging science – namely affecting the immune system so that it mounts a proper immune response.
An exhaustive account of the number and types of plants that are immune modulating would take volumes, but here are some brief examples:
• Ginger influences both cell-mediated immune response and nonspecific proliferation of T lymphocyte, and may exert beneficial effects in a number of clinical conditions, such as chronic inflammation and autoimmune diseases. (3)
• Garlic can modulate the activity of several metabolizing enzymes that activate and detoxify carcinogens and inhibit DNA adduct formation, antioxidative and free radicals scavenging properties and regulation of cell proliferation, apoptosis and immune responses. Recent data show that garlic-derived products modulate cell-signaling pathways in a fashion that controls the unwanted proliferation of cells thereby imparting strong cancer chemopreventive as well as cancer therapeutic effects.(4)
• African geranium can improve immune functions at various levels, hence, validating its medicinal uses. (5)
• Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction.(6)
• The mistletoe (Viscum album L.) extract Iscador has been shown to be an effective complementary drug in the treatment of cancer patients after surgical removal of the primary tumor. In animal tests, clear anti-carcinogenic effects of Iscador were demonstrated as reduction of tumor growth in preformed tumors and as prevention of tumor growth in newly induced tumors. Mainly immune stimulation but also direct cytotoxic activity are believed to be responsible for the anti-carcinogenic activity of Iscador.(7)
• Ginseng, the root of Panax species, is a well-known herbal medicine that has been used as a traditional medicine in China, Korea, and Japan for thousands of years. Current in vivo and in vitro studies have shown its beneficial effects in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency, and hepatotoxicity. In general, antioxidant, anti-inflammatory, anti-apoptotic, and immune-stimulatory activities are mostly underlying the possible ginseng-mediated protective mechanisms.(8)
Learnings from Plants?
Since plants have immune modulating effects in people and have been used to fight diseases for thousands of years, it raises the question – is there anything that “nature’s pharmacy” can teach us when it comes to immunotherapy and cancer?
Apparently there is – Synergism. If one reviews the actual biological mechanisms of plants it is apparent that their efficacy is probably the result of the varied, interdependent, and independent biological pathways in which they act. For example, many medicinal plants may possess some or all of the following properties: antioxidant, anti-inflammatory, direct cytotoxic, differentiation, detoxification, apoptotic, and immune-stimulatory. How many man-made immune therapies can do all of this simultaneously?
This may be the most important lesson of all – that efficacy is due to a multi-modality approach. The synergies used by plants in killing cancer cells, moving them towards apoptosis, stimulating the immune system, reducing inflammation, detoxifying, and affecting free radicals may in fact be the only way to control and ultimately cure cancer.
If this is correct, the orthodox reductionist view of manipulating one biological mechanism in a human system may never prove sufficient to create durable cures. It also means that the standard approach used by science to identify, isolate and ultimately synthesize specific molecules taken from plants is unwise. Instead, it should be recognized that molecules work together, stimulating complimentary or synergistic pathways and therefore should not be pulled apart. Despite the economic disincentives that exist to view plants as potential cancer therapy, perhaps it is time to do just that. Wouldn’t it be ironic if safe and effective multi-modality immune therapies for cancer were already in existence?
“Let thy food be thy medicine and thy medicine be thy food.” – Hippocrates (460-377 B.C.)
“The art of healing comes from nature and not from the physician. Therefore, the physician must start from nature with an open mind.” – Paracelsus
(1) Much of the information about the immune system comes from the National Institute of Allergy and Infectious Diseases (NIAID)
(2) These may include: a dysfunction of the host’s immune system which allows tumors to evade immunosurveillance from T cell anergy, the existence of regulatory T cells, and systemic defects of dendritic cells derived from tumor patients. In addition, escape from immunosurveillance can also be linked to tumor-related factors, including secretion of immunosuppressive cytokines, resistance to apoptosis, and deficient expression of immunomodulatory molecules and major histocompatibility complex (MHC) class I antigens possibly due to immunoselection.
(3) Zhou HL, et al., The modulatory effects of the volatile oil of ginger on the cellular immune response in vitro and in vivo in mice. J Ethnopharmacol. 2006 Apr 21;105(1-2):301-5.
(4) Shukla Y, and Kalra N., Cancer chemoprevention with garlic and its constituents. Cancer Lett. 2006 Jun 20.
(5) Kolodziej H and Kiderlen AF., In vitro evaluation of antibacterial and immunomodulatory activities of Pelargonium reniforme, Pelargonium sidoides and the related herbal drug preparation EPs((R)) 7630. Phytomedicine. 2007;14 Suppl 1:18-26.
(6) Vucenik I, and Shamsuddin AM., Protection against cancer by dietary IP6 and inositol., Nutr Cancer. 2006;55(2):109-25.
(7) Maldacker J., Preclinical investigations with mistletoe (Viscum album L.) extract Iscador. Arzneimittelforschung. 2006 Jun;56(6A):497-507.
(8) Radad K, et al., Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci. 2006 Mar;100(3):175-86.