Cancer Vaccines and Immunotherapy-3

Antioxidants (Vitamins C and E). Supplementing the diet of colorectal cancer patients with high doses of vitamin E (750 mg per day) for two weeks increased lymphocyte numbers and improved the lymphocytes’ ability to produce messengers (interleukin-2 and interferon gamma) that are associated with the type of immune response required to destroy cancer cells (Malmberg KJ et al 2002). Therefore, high-dose vitamin E supplements may be considered to support the use of cancer vaccines and immunotherapy. Long-term supplementation at lower doses of 100 to 200 mg a day has improved immune function (Calder PC et al 2002b; Pallast EG et al 1999).

Vitamin C supplements also improve immune function and protect lymphocytes against damage (Lenton KJ et al 2003; Schneider M et al 2001).

Folic Acid. Deficiencies in folic acid impair the immune system by reducing the ability of CD8 T cells to divide and increase in number (Courtemanche C et al 2004). In addition, low levels of folic acid lead to genetic instability in lymphocytes and increased cell death, or apoptosis (Courtemanche C et al 2004; Duthie SJ et al 1998). However, the impairment of lymphocyte function can be restored by folic acid supplements (Courtemanche C et al 2004).

Vitamin B12. Vitamin B12 plays a key role in immune function, as B12 deficiencies in humans lead to low numbers of CD8 T cells and impair the activity of natural killer cells (Tamura J et al 1999). These cells are essential for the cytotoxic arm of the immune system, which in turn is essential for destroying cancer cells. Supplementing with B12 restores CD8 T-cell numbers and natural killer cell activity (Tamura J et al 1999).

Vitamin B6. Deficiencies in vitamin B6 impair the immune system and are associated with a reduced ability of lymphocytes to produce messengers (cytokines) required for sustained immune activation (Doke S et al 1998).

Selenium. Selenium supplements (100 mcg a day) improve immune cell function by increasing the cells’ ability to produce messengers (cytokines) associated with the type of immune responses required to clear tumor cells (Broome CS et al 2004).

Glutamine. Glutamine supplements (30 grams a day) sustain immune cell function (Yoshida S et al 1998). Clinical studies have shown glutamine supplements to be particularly effective in counteracting immunosuppression associated with surgery (Calder PC et al 1999; O'Riordain MG et al 1996), and thus to be of benefit to patients undergoing an immunotherapy/vaccination regimen after surgical removal of the tumor.

Ginseng. The medicinal herb ginseng improves immune cell function (Larsen MW et al 2004). Of particular importance to the successful use of cancer vaccines is the recently reported ability of ginseng products to drive the development of dendritic cells that are essential for successful cancer vaccination (Takei M et al 2004).

Melatonin. Melatonin hormone supplements (20 mg a day, at bedtime) improve lymphocyte function and have been tested in clinical studies of blood cancers (El-Sokkary GH et al 2003; Lissoni P et al 2000).

Garlic. Garlic extracts boost the activity of natural killer cells against tumor cells (Hassan ZM et al 2003).

Mushroom Extracts (AHCC). Extracts from various mushrooms boost immune cell function (Kidd PM 2000). In particular, active hexose correlated compound (AHCC) improves the function of natural killer cells and confers benefits to liver cancer patients after surgical removal of the tumor (Matsui Y et al 2002).

Omega-3 Fatty Acids. The ratio of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) modulates the inflammatory response. Inflammatory cells typically contain high levels of arachidonic acid and low levels of omega-3 PUFA (Calder PC 2002, 2002a). Increasing omega-3 fatty acid intake antagonizes arachidonic acid levels in inflammatory cell membranes, and decreases the amount of arachidonic acid that is available for production of pro-inflammatory arachidonic acid-derived mediators (Calder PC 2003).

Omega-3 PUFA may have indirect immunomodulatory activity mediated through tumor necrosis factor-alpha (TNF-a) and nuclear factor-kappa beta (NF-?B) production (Babcock TA et al 2002). Administration of omega-3 fatty acids before and after surgery (prior to immunotherapy) may have a favorable effect on outcome by lowering the magnitude of inflammatory response and preventing immune suppression (Weiss G et al 2002). Fatty fish such as salmon, mackerel, tuna, and herring are good sources of long-chain omega-3 PUFA.

Tracking Your Progress

Monthly Blood Tests. A range of blood tests and other diagnostic procedures can be used to monitor the effectiveness of cancer immunotherapy. Results from these tests provide information required to assess the effectiveness of this new treatment modality.

The following tests are essential for monitoring the effectiveness of immunotherapy.

Tumor antigen profile: determining the antigens (abnormal proteins) produced by each tumor is important in assessing the use of cancer vaccines or other forms of immunotherapy as a treatment choice. Tumor antigen profile should also be monitored during immunotherapy, as the tumor can develop variations that stop the display of these antigens as a means of escaping detection.

Immune cell function: the function of lymphocytes is monitored during cancer immunotherapy by a variety of techniques. These include proliferation assays to assess their ability to expand in response to activation, and cell-kill (cytotoxic) assays to assess the ability of CD8 lymphocytes to kill tumor cells (Clay TM et al 2001; Keilholz U et al 2002b; Lyerly HK 2003).

PSA: prostate-specific antigen can be detected in blood samples from prostate cancer patients and has been established as a reliable marker for disease progression or patient response to therapy (Coetzee LJ et al 1996; Kiper A et al 2005). Prostate cancer patients treated with cancer vaccines in clinical studies showed reductions in their PSA levels (Noguchi M et al 2004b; Noguchi M et al 2004a).

CEA: monitoring of serum levels of carcinoembryonic antigen is recommended for colorectal cancer patients as a marker for disease progression or response to treatment (Sunga AY et al 2005).

Angiogenesis markers: angiogenesis is the process of forming new blood vessels, which is essential for tumors to spread to other parts of the body. Increased levels of the angiogenic factor vascular endothelial growth factor (VEGF) in the blood of cancer patients serves as a robust indicator of disease progression and can be used to monitor response to treatment with cancer immunotherapy (Bonfanti A et al 2000; Brostjan C et al 2003; Poon RT et al 2001). Circulating endothelial cells, detectable in the blood of cancer patients, are increased and have also been established as another indicator of disease progression (Beerepoot LV et al 2004; Mancuso P et al 2003).

Growth factors: serum levels of the growth factors pleiotrophin (PTN) and fibroblast growth factor-2 (FGF-2) are increased in prostate cancer patients and can be used as a marker for disease progression or response to therapy (Aigner A et al 2003).

Immunosuppressive agents: levels of tumor-produced immunosuppressive agents (for example, interleukin-10 (IL-10) (Sarris AH et al 1999) and transforming growth factor-beta (TGF-ß) (Junker U et al 1996)) can be detected in patients’ serum and used to check for disease progression or response to treatment.

X-rays and scans: can be used to monitor the response or progression of disease during cancer immunotherapy.

Physical examination: regular physical examinations can detect changes in body mass and enlarged lymph nodes that may be signs of disease progression (Sunga AY et al 2005).
For More Information
Cancer immunotherapy patients may wish to read the following chapters and design a program that addresses the full range of their cancer problems:

a)Complementary Adjuvant Cancer Therapies

b)Cancer Surgery

c)Immune System Enhancement

d)Blood Disorders

e)Medical Testing.

The National Cancer Institute Clinical Trials Database lists and describes ongoing clinical trials at different locations throughout the US. This can be accessed at the website http://cancertrials.nci.nih.gov/ or by calling the Cancer Information Service at 1-800-4-CANCER.

The American Cancer Society, 1-800-ACS-2345.


Life Extension Foundation Recommendations

Patients should ask their physicians for assistance in obtaining information on ongoing cancer vaccine and other immunotherapy clinical studies, and the criteria for subject enrollment and participation. Immunotherapy patients should consult their physicians before starting to use any nutritional supplements while receiving treatment. In addition, if using nutritional supplements, they should ask their physicians for assistance in ensuring the implementation of blood tests and diagnostic procedures that are essential in monitoring the effectiveness of any adjuvant therapy for cancer.

Some guidelines for using nutritional supplements with immune-boosting cancer therapies include:

1)Zinc—20 to 50 milligrams (mg) daily (Hercberg S et al 1998; Kohn S et al 2000)

2)Vitamin C—120 mg daily (Hercberg S et al 1998)

3)Vitamin E—800 international units (IU) of d-alpha tocopheryl succinate daily for two weeks (Malmberg KJ et al 2002); 400 IU daily for long-term use (Calder PC et al 2002b; Pallast EG et al 1999)

4)Folic acid—800 micrograms (mcg) daily (Fenech M 2001)

5)Vitamin B12—7 mcg daily (Fenech M 2001)

6)Vitamin B6—2.1 to 2.7 mg (one B-complex capsule) daily (Kwak HK et al 2002)

7)Selenium—100 mcg daily (Broome CS et al 2004)

8)Glutamine—30 grams (g) daily (Yoshida S et al 1998)

9)Ginseng, panax—100 mg daily (Anderson GD et al 2003)

10)Melatonin—20 mg daily, at bedtime (Lissoni P et al 2000)

11)Garlic—250 mg daily (Dhawan V et al 2004)

12)Mushroom extract—active hexose correlated compound: 3 g daily (Matsui Y et al 2002)

13)Fish oil—containing EPA: 4.7 g daily (Kew S et al 2004).

Note that most cancer patients take higher doses of vitamin C (2000 to 20,000 mg/day), selenium (200 to 400 mcg/day), vitamin B6 (100 to 750 mg/day), and vitamin B12 (100 to 300 mcg/day). These doses are considerably higher than the doses used in the studies cited above.


Blood Test Availability

Tests for PSA, CEA, selenium, vitamin B12, and folate serum levels are available via Life Extension/National Diagnostics, Inc., and may be ordered on line.
Tumor antigen profile can be determined via Genzyme Genetics (http://www.genzymegenetics.com) and may be ordered by a physician by calling 1-800-966-4440.

Tests for immune cell function, serum growth factor levels, and immunosuppressive agents (IL-10) are available at UCLA’s Jonsson Comprehensive Cancer Center (http://www.cancer.mednet.ucla.edu/).

X-rays, scans, and physical examinations can be arranged through your physician.

Cancer Vaccines and Immunotherapies Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

EPA/DHA

Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.
Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Folic acid

Consult your doctor before taking folic acid if you have a vitamin B12 deficiency.
Daily doses of more than 1 milligram of folic acid can precipitate or exacerbate the neurological damage caused by a vitamin B12 deficiency.

Garlic

Garlic has blood-thinning, anticlotting properties.
Discontinue using garlic before any surgical procedure.
Garlic can cause headache, muscle pain, fatigue, vertigo, watery eyes, asthma, and gastrointestinal symptoms such as nausea and diarrhea.
Ingesting large amounts of garlic can cause bad breath and body odor.

Ginseng

Consult your doctor before taking ginseng if you have high blood pressure. Overuse of ginseng can increase blood pressure.
Consult your doctor before taking ginseng if you take nonsteroidal anti-inflammatory drugs (NSAIDs) and/or warfarin (Coumadin). Taking NSAIDs or warfarin with ginseng can increase the risk of bleeding.
Consult your doctor before taking ginseng if you have diabetes. Taking ginseng can cause an extreme drop in your blood glucose level. Ginseng can cause breast pain, vaginal bleeding after menopause, insomnia, headaches, and nosebleeds.

L-Glutamine

Consult your doctor before taking L-glutamine if you have kidney failure or liver failure.
L-glutamine can cause gastrointestinal symptoms such as nausea and diarrhea.

Melatonin

Do not take melatonin if you are depressed.
Do not take high doses of melatonin if you are trying to conceive. High doses of melatonin have been shown to inhibit ovulation.
Melatonin can cause morning grogginess, a feeling of having a hangover or a “heavy head,” or gastrointestinal symptoms such as nausea and diarrhea.
Selenium

High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.
High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.
Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin B6

Individuals who are being treated with levodopa without taking carbidopa at the same time should avoid doses of 5 milligrams or greater daily of vitamin B6.

Vitamin B12 (cyanocobalamin)

Do not take cyanocobalamin if you have Leber's optic atrophy.

Vitamin C

a)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

b)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E
a)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

b)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

c)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

e)Discontinue using vitamin E 1 month before any surgical procedure.

Zinc

a)High doses of zinc (above 30 milligrams daily) can cause adverse reactions.

b)Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.

c)High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.

d)High doses of zinc may suppress the immune system.