Natural Biological Response Modifier MGN-3
Shown to be Effective Against Tumor Cell Growth

More than 150 different types of white blood cells have been identified, and of these, natural killer
(NK) cells are one of the most common, representing up to 15 per cent of total white blood cells.
They are important because, unlike other white blood cells, they are able to work more or less
independently, not requiring special instructions from the immune system in order to recognize or
attack a foreign cell. For this reason, they are often considered the body’s first line of defense
against cancer and viral-infected cells.

Circulating the body through the blood and lymph systems, the majority of NK cells are in a resting
state. They become more active and aggressive in response to immuno-regulatory proteins called
cytokines, which are chemical messengers that promote immune activity. Once activated, NK cells
become quite aggressive in their search-and-destroy activities. Upon encountering a tumour cell,
the activated NK cell attaches to the membrane of the cancer cell and injects toxic granules that
quickly dissolve the target cell. In less than five minutes, the cancer cell is dead and the NK cell
moves on to its next victim. A single NK cell can destroy up to 27 cancer cells before it dies.

The absolute number of NK cells present in the blood gives little indication of the efficiency of
immune function. Instead, it is the activity of the NK cells (how aggressive they are in recognizing
and binding to tumour cells) that is important. Research has shown that MGN-3 can dramatically
increase the activity of NK cells in cancer patients by up to 500 percent, and most importantly,
“without overstimulating the immune system”.

Solid data from human clinical trials offers compelling evidence that MGN-3 has enormous
promise as an immune-enhancing therapy in the treatment of cancer and other diseases.
Research also shows that MGN-3 can inhibit replication of the HIV virus without damaging healthy
cells, and studies have suggested that it may also be useful in the treatment of hepatitis C.

MGN-3 is completely non-toxic and can safely be used in conjunction with conventional treatment,
including chemotherapy and radiation, both to increase the effect of the therapy and to decrease
adverse side-effects.

Natural Biological Response Modifier MGN-3
Shown to be Effective Against Tumor Cell Growth

1. To examine the action of MGN-3, a natural Biological Response Modifier (BRM), against
tumor cell growth

2. To gain an understanding of the role of BRMs in the treatment of cancers

3. To explore the role(s) of MGN-3 immunotherapy in the treatment of cancer

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Enhancment of immune system

Recent advances in research on MGN-3 showed that in addition to having potent immunomodulatory
function and anti-HIV activity, this compound can be effective in directly targeting certain cancer cells.
MGN-3 is a new biological response modifier (BRM) that is an arabinoxylan compound which is a
polysaccharide containing hemicellulose extract of rice bran modified by enzymes from Shiitake
mushrooms.

In the present preliminary study, the direct effects of MGN-3 on skin cancer cell growth and cytokine
production were evaluated. Incubation of a squamous cell carcinoma [SCC13] cell line with MGN-3
arrested tumor cell growth (30% decrease in cell number after 48 hours and 50% at 72 hours of
culture) as compared to control SCC13 cells grown in a MEM media alone which continued to
increase in cell number.

Employing flow cytometry procedures, analyses showed that after 16 hours of treatment of SCC13
cells with MGN-3, there was a five-fold increase in intracellular levels of interleukin 10 [IL-10], but no
apparent change in content of interferon-y [INF-y]. ELISA analyses showed higher (8-fold) levels of
IL-10 and a 3-fold increase in IL-121 in the culture media of SCC13 cells. However, little change in
INF-y concentration was detected. The effects of MGN-3 on other cell lines, such as normal and tumor
breast cells and prostate cancer cells, were also evaluated.

In conclusion, our findings indicate that MGN-3 acts by not only enhancing the host immune function
but also through a direct alteration of tumor cell growth and production of cytokines. These findings
may offer a mechanism of action which could explain the high clinical success and impressive benefits
of MGN-3 treatment observed with 32 patients over 4 years.

MGN-3 was provided by Daiwa Pharmaceuticals Company, Ltd., Tokyo, Japan. Supported in part by
VA Medical Research Funds and by funds provided by Daiwa Pharmaceuticals Company, Ltd.

by Mamdooh Ghoncum, PhD, Chief of Research, Dept. of Otolaryngology, Drew University of Medical Science; Memdooh
Ghoneum, PhD, Ken H. Tachiki, PhD; Koichi Uyemura, PhD; Takashi Makinodan; Nalini Makhigani; and Dean Yamaguchi, MD,
PhD   

Goals and Objectives:

Increased NK Activity
Shows Dramatic Results
Against Cancer and Viral Infections

MGN-3 is a polysaccharide composed of the fibrous part of rice bran extract that has been modified
by enzymes from shiitake mushrooms. MGN-3 has antiviral activity that enhances the body’s
immune response against viral-infected cells. In seven published studies involving a total of 72
human subjects, the efficacy of MGN-3 equals or surpasses the very best immune-modulating drugs
available but, in contrast, exhibits a complete lack of toxicity.

NK Cells in Cancer Treatment

Abstract