The following may have errors due to the scanning process, but should be a good start for further research by those interested

CLINICAL RESEARCH USING MGN-3
(ARABINOXYLANE COMPOUND)
IMMUNOMODULATORY AND ANTI·CANCER PROPERTIES OF (MGN·3), A MODIFIED XYLOSE FROM RICE BRAN, IN 5 PATIENTS WITH BREAST CANCER
Ghoneum M.
Cancer: The Interface Between Basic and Applied Research November 5·8,1995 Baltimore, MD
MGN·3 is a new biological response modifier (BRM). It is an extract of arabinoxylane from rice bran that has been enzymatically modified to increase it's immunomodulatory function. Five patients with breast cancer were given MGN-3 at 3g/d, then NK cell activity was measured by 4·hr. 51Cr·release assay using K562 tumor cells as targets.
Resu Its showed that:
patients had low level of basal NK activity (13.5·34.9%), at effector to target (E:T) ratios of 12 and 100:1, that was significantly enhanced by MGN-3 treatment (21.1·50.1%) at the same E:T ratios.
The augmentation in NK activity was detected as early as 1-2 weeks post treatment and was fu rther increased with continuation of administering MGN·3.
Two patients who participated early in the study (6·8 mon.) are in complete remission. We conclude the high augmentory effect of MGN·3 on NK cells and the absence of notable side effects make MGN-3 a promising BRM. In addition, immunotherapeutic effect of MGN-3 in conjunction with chemotherapy may be useful in treatment of cancer patients. MGN·3 was offered by Daiwa Pharmaceutical Co., Ltd. 1-16-19, Sangenjaya,Setagaya.
ANTI-HIV ACTIVITY BY MGN-3, IN VITRO
Ghoneum, M.
XI International Conference on AIDS
July 7-12,1996, Vancouver, BC
Obiectiv~
To examine the effect of MGN·3 on HIV induced syncytia formation (SF) In Vitro. MGN·3 is an arabinoxylane from rice bran, that is enzymatically treated with an extract from Hyphomycetes mycelia.
Method
Peripheral Blood lymphocytes (PBl) from AIDS patients were cultured with PHA in the presence or absence of different concentrations of MGN-3 (12.5-100 ug/ml) for 7 days. The number of synctia were evaluated, and the size of each was also recorded. The effect of MGN·3 on PHA induced PBl proliferation was studied by MTI assay.
Results
Treatment with MGN·3 resulted in:
Significant inhibition in the SF.
The effect was dose dependent, percentage of inhibition in SF was 38.5, 50, 62.5, and 75% at concentrations of 12.5, 25, 50, and 100 ~g/ml respectively;
Complete absence of SF having large and medium size post treatment, and
4) MGN-3 caused 25·30% inhibition of PBl proliferation
Conclusion
We conclude that MGN-3 is a natural product that possesses a potent effect against synctia formation by HIV. This property of MGN-3 may be of poten­tial value in therapy of HIV infection.
EFFECT OF MGN·3 ON HUMAN NATURAL KILLER CEll ACTIVITY AND INTERFERON·y SYNTHESIS IN VITRO
Ghoneum M., Namatalla G., and Kim C.
FASEB JOURNAL
June 2·6, 1996, New Orleans, lA
MGN·3 is an extract of arabinoxylane from rice bran that has been enzymatically treated with an extract from Hyphomycetes mycelia. In this study we investigated the effect. MGN-3 on natural killer (NK) cell activity and interferon-y (IFN·y) synthesis by peripheral blood mononuclear cells (MNC). MNC was prepared from peripheral blood of healthy individuals and incubated with various concentrations of MGN·3 for 16 hrs., and then NK cell activity was measured by 4 hr. Cr·release assay using K56 Tumor cells as target NK activity was significantly enhanced (2·5 fold) by treatment with MGN-3 at 0-100 ug/ml. In an attempt to investigate the mechanism by which MGN-3 enhances NK activity, we examined the effect of MGN-3 on IFN·y production by MNC. Culture supernatants of the cells incubated with MGN-3 were collected and analyzed for INF·y synthesis by ELISA. INF-y production was increased >2 fold. We concluded that MGN-3 is a potent biological response modifier (BRM) and may be useful in immunotherapy of cancer. MGN·3 was offered by Daiwa Pharmaceutical Co. Ltd. Tokyo-Japan.
NK IMMUNORESTORATION OF CANCER PATIENTS BY MGN·3, A MODIFIED ARABINOXYLANE RICE BRAN
(Study of 32 Patients Followed for up to 4 Years).
Ghoneum M. and Jim Brown.
Drew University of Medicine and Science,
Department of Otolarynngology
NK cells have been characterized as non·B cells or non·T cells lacking the characteristics of mature macro phages which develop from the bone marrow independently of thymic influence. NK cells playa crucial role in tumor rejection, immune surveillance, resistance to infections, and immune regulation. NK cell destruction of cancer cells involves a sequence of events. First, the NK cells recognizes and binds to the cancer cell. This process requires receptor-to-receptor interaction. Next, the NK cell releases granules which penetrate the cancer cell and ultimately kill it. The NK cell is then free to bind to another cancer cell and repeat the same process.
However, cancer cells know how to fight back in a sort of cell war. We found for the first time in our laboratory that cancer cells can destroyWBCs through the phenomenon of phagocytosis. We have observed three ways in which this is done. The cancer cell can extend two arms around the WBC or it can develop a cup-shaped opening where the WBC is drawn inside. A third way is for the cancer cell to extend a long arm to capture the WBC and finally draw it inside the cancer cell where it is digested. In addition, extensive work by others has shown that cancer cells secrete immune· suppressive substances which inhibit the function of the immune system.
Many attempts have been made in the last 25 years to strengthen the power of the immune system using different biological response modifiers (BRMs). These are substances originating from bacteria and fungi which possess immunoaugmentory properties. In addition, some kinds of cytokines serve as BRMs such as interferons, interleukin-2 and interleukin-12. There are two problems associated with these BRMs: 1 st) toxicity and 2nd) the development of hyporesponsiveness in which a single administration of the BRM can significantly enhance NK cell activity, but that repeated administration of the same BRM results in depression of NK cell activity. It is interesting to note that MGN-3 has advantages over other BRMs. It is nontoxic and has not shown hyporesposiveness in the four years that the patients have been followed. This work was undertaken in order to investigate the augmentory effect of a new BRM known as MGN-3 on NK cell function and T and B cell proliferation in 32 patients. Tumor·associated antigens were reported for selected patients.

CLINICAL RESEARCH USING MGN-3
(ARABINOXVLANE COMPOUND)
NK IMMUNOMODULATORY FUNCTION IN 27 CANCER PATIENTS BY MGN-3, A MODIFIED ARABINOXYLANE FROM RICE BRAN
Ghoneum M. Namatalla G.
87th Annual Meeting of the American Association for Cancer Research
April 20-24, 1996 Washington, DC
MGN-3 immunomodulatory function was examined in 27 cancer patients. MGN-3 is an arabinoxylane from rice bran that has been enzymatically modified by hyphomycetes mycelia. The patients had different types of advanced malignancies: 7 patients had breast CA, 7 prostate, 8 multiple myelome (MM), 3 leukemia, and 2 cervical. All patients were under treatment with conventional therapy and were also given 3g of MGN-3 daily. NK activity was examined at 2 weeks, 3 months and 6 months. Activity of NK cells was examined by 51Cr-release assay using K562 tumor cells as targets, at effector:target ratios from 12:1-100:1.
Results showed that:
Patients had low level of basal NK activity (10.8-40%),
treatment with MGN-3 caused a remarkable increase in NK activity at 2 weeks. The percentages of induction were as follows: breast Ca 154-332%, prostatic 174-384%, leukemia 100-240%, MM 100-537%, and cervical CA 100-275%,
enhancement of NK activity continues to rise at 3 and 6 months after treatment.
We conclude that the high augmentory effect of MGN-3 makes it a promising immunotherapeutic agent for treatment of cancer.
SYNERGISTIC EFFECT OF MODIFIED ARABINOXYLANE (MGN-3) AND LOW DOSE OF RECOMBINANT IL-2 ON HUMAN NK CELL ACTIVITY AND TNF PRODUCTION
Ghoneum M. Jewett A.
American Academy of Anti-Aging Medicine, Educational Conference
August 15-16, 1998 East Rutherford, NJ
We have recently shown the potent biological response modification of a new product called MGN-3, an arabinoxylane from rice bran that has been modified by extract from Hyphomycetes mycelia. MGN-3 possesses anti-HIV activity, NK immunomodulation and anti-cancer activity. Success with recombinant 1l:2 (rll:2) immunotherapy of human cancer appears to depend on the administration of high doses, which are frequently associated with excessive toxicity. Therefore certain modifications are greatly needed on the use of rll:2 at low doses without significant loss of anti-tumor efficacy. Experiments were designed to examine NK activity post culture human peripheral blood lymphocytes (PBL) with MGN-3 alone (1 mg/ml), rll:2 alone (500u/ml) and MGN-3 (1 mg/ml) plus r1L-2 (500u/ml). Results showed that MGN-3 and r1L-2 increase NK activity by 138.6% and 179.5% respectively. Interestingly a synergistic effect on NK activity was noticed post culture of PBL with MGN-3 and rll:2 (332.7% of control). The mechanism underlying this phenomenon is not fully understood but could be attributed to action of MGN-3 on TNF-a production. Results showed that TNF-a levels from control untreated PBL of 20 subjects was 195 pg/ml +/- 102. Treatment with rll:2 showed no change in TNF-a level (216pg/ml +/- 100), while MGN-3 significantly increased TNF-a production (5773pg/ml +/- 2653). On the other hand, a synergistic effect of MGN-3 plus r1L-2 resulted in a further increase of TNF-a production (8127pg/ml +/- 2587). We conclude that; I) MGN-3 is a potent TNF-a producer, and 2) the immunomodulatory function by low concentration of rll:2 on anti-tumor activity by NK cells could be greatly augmented by the concomitant use of MGN-3.
ENHANCEMENT OF HUMAN NATURAL KILLER CELL ACTIVITY BY MODIFIED ARABINOXYLANE FROM RICE BRAN (MGN-3)
Ghoneum M.
INTERNATIONAL JOURNAL OF IMMUNOTHERAPY XIV (i) (1998)
Summary: Arabinoxylane, from rice bran (MGN-3) was examined for its augmentory effect on human natural killer cell activity in vivo and in vitro. Twenty-four individuals were given MGN-3 orally at three different concentrations: 15, 30 and 45 mg/kg/day for 2 months. Peripheral blood lymphocyte-natural killer cell activity was tested by 51CR-release assay against K562 and Raji tumor cells at 1 week, 1 month and 2 months post-treatment and results were compared with baseline natural killer activity. Treatment with MGN-3 enhanced natural killer activity against K562 tumor cells at all concentrations used. In a dose-dependent manner, MGN-3 at 15 mg/kg/day increased natural killer activity after 1 month post-treatment (two-fold over control value), while significant induction of natural killer activity at 30 mg/kg/day was detected as early as 1 week post-treatment (2 1/2 times control value). Natural killer cell activity continued to increase with continuation of treatment and peaked (five-fold) at 2 months (end of treatment period). Increasing the concentration to 45 mg/kg/day showed similar trends in natural killer activity. However the magnitude in values was higher than for 30 mg/kg/day. After discontinuation of treatment, natural killer activity declined and returned to baseline value (14 lytic units) at 1 month. Enhanced natural killer activity was associated with an increase in the cytotoxic reactivity against the resistant Raji cell line. MGN-3 at 45 mg/kg/day showed a significant increase in natural killer activity after 1 week (eight-fold) and peaked at 2 months post-treatment (27 times that of baseline). Culture of peripheral blood lymphocytes with MGN-3 for 16 hours demonstrated a 1.3 to 1.5 times increase in natural killer activity over the control value. The mechanism by which MGN-3 increases natural killer activity was examined and showed no change in cluster of differentiation (CD) 16+ and C056+ CD3- of MGN-3 activated natural killer cells as compared with baseline value; a four-fold increase in the binding capacity of natural killer to tumor cell targets as compared with baseline value; and a significant increase in the production of Interferon-y (340-580 pg/ml). Postculture of peripheral blood lymphocytes with MGN-3 at concentrations of 25-100 ~g/ml. Thus, MGN-3 seems to act as a potent immunomodulator causing augmentation of natural killer cell activity, and with the absence of notable side-effects, MGN-3 could be used as a new biological response modifier having possible therapeutic effects against cancer.
ANTI-HIV ACTIVITY IN VITRO OF MGN-3,
AN ACTIVATED ARABINOXYLANE FROM RICE BRAN
Ghoneum M.
XI International Conference on AIDS JULY 7-12,1996, Vancouver BC
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 243,25-29 (1998), ARTICLE NO RC978047
MGN-3, an arabinoxylane from rice bran that has been enzymatically modified with extract from hyphomycetes mycelia, was tested for anti-HIV activity in vitro. MGN-3 activity against HIV-l (SF strain) was examined in primary cultures of peripheral blood mononuclear cells. MGN-3 inhibited HIV-I replication by: (1) inhibition of HIV-l p24 antigen production in a dose dependent manner; MGN-3 at concentrations of 12.5, 25, 50 and 100 ug/ml showed 18.3, 42.8, 59 and 75% reduction in p24 antigen, respectively; and (2) inhibition of syncytia formation maximized (75%) at concentrations of 100 ug/ml. Further studies showed that ingestion of MGN-3 at concentration of 15 mg/kg/day resulted in a significant increase in T and B cell mitogen response at 2 months after treatment: 146% for PHA, 140% for Con A and 136.6% for PWM mitogen. We conclude that MGN-3 possesses potent anti-HIV activity and in the absence of any notable side effects, MGN-3 shows promise as an agent for treating patients with AIDS.
1998 Academic Press.

One Sizeable Step for Immunology, One Giant Leap for Cancer Patients
by Mamdooh Ghoneum, PhD
Associate Professor and Chief of Research, Department of Otolaryngology, Charles D. Drew University; Research Associate, Department of Neurobiology, UCLA School of Medicine
Background
Although cymclsm and dis­illusionment with the failed "war against cancer" are widespread, I remain very optimistic that we will triumph over this seemingly invincible killer. Given the disappointing results and many drawbacks of cytotoxic therapies, it seems clear that our best hope for a decisive victory against cancer lies in immuno-augmentive therapies ~ those that enhance the body's innate immune response to cancer cells.
As a research immunologist, I have spent 18 years studying immuno­modulating substances - natural compounds derived from mushrooms, herbs, fungi, and bacteria, as well as synthetic drugs like Interleukin-2 and interferon. Approximately six years ago, I stumbled across a natural substance that was so promising, so profoundly superior to everything else I had ever evaluated, that I abandoned all other projects, including NIH-funded research, in order to focus entirely on this substance.
The product, MGN-3 (an
arabinoxylane compound), is a polysaccharide composed of the hemicellose-J3 extract of rice bran,
modified by enzymes from Shiitake mushrooms. As we have detailed in 7 previously published studies, involving a total of 72 human subjects, the efficacy ofMGN-3 equals or surpasses the very best immune-modulating drugs available but, in stark contrast to these, exhibits a complete lack of toxicity. (Copies of complete research papers and data on MGN-3 can be obtained from Lane Labs at 201-236-9090,)
Much of the data regarding MGN-3 has been previously published in technical journals and presented at international research conferences, but the information remains largely unknown to oncologists and other health professionals dealing directly with the cancer patient. The aim of this article is to bring this research to the attention of the practicing clinician, to summarize what is known about the actions of MGN-3, and explore its present role in the treatment of cancer patients.
Anti-viral activity: In addition to very encouraging results using MGN-3 in the treatment of malignancies, other research suggests a promising role for MGN-3 as a therapy for HIV, Hepatitis C, and other viral infections. MGN-3 has antiviral activity and also enhances the

body's immune response against virally­infected cells. In vitro research shows that MGN-3 inhibits replication of the HIV virus without cytotoxicity in a dose­dependent manner.' Human studies suggest that MGN -3 may also be extremely useful in the treatment of Hepatitis C. In these patients liver enzymes return to normal levels within 1-8 weeks of treatment with MGN-3. The results of our ongoing clinical research into the antiviral applications of MGN-3 will be the subject of future reports.
The role of NK cells in the treatment of cancer
Over 150 different types of white blood cells have been identified and, of these, NK cells are one of the most common, representing up to 15% oftotal 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 to be the body's first line of defense against cancer and viral­infected cells.
Photo #1:
NK cell (top) attaching to a cancer cell.
Photo #2:
The cancer cell is dissolved and the NK cell moves on to another cancer cell.
TOWNSEND LETTER for DOCTORS & PATIENTS - JANUARY 2000
/

One Sizeable Step for Immunology, One Giant Leap for Cancer Patients
by Mamdooh Ghoneum, PhD
Associate Professor and Chief of Research, Department of Otolaryngology, Charles D. Drew University; Research Associate, Department of Neurobiology, UCLA School of Medicine
Background
Although cymclsm and dis­illusionment with the failed "war against cancer" are widespread, I remain very optimistic that we will triumph over this seemingly invincible killer. Given the disappointing results and many drawbacks of cytotoxic therapies, it seems clear that our best hope for a decisive victory against cancer liesin immuno-augmentive therapies ­those that enhance the body's innate immune response to cancer cells.
As a research immunologist, I have spent 18 years studying immuno­modulating substances - natural compounds derived from mushrooms, herbs, fungi, and bacteria, as well as synthetic drugs like Interleukin-2 and interferon. Approximately six years ago, I stumbled across a natural substance that was so promising, so profoundly superior to everything else I had ever evaluated, that I abandoned all other projects, including NIH-funded research, in order to focus entirely on this substance.
The product, MGN-3 (an
arabinoxylane compound), is a polysaccharide composed of the hemicellose-J3 extract of rice bran,
modified by enzymes from Shiitake mushrooms. As we have detailed in 7 previously published studies, involving a total of 72 human subjects, the efficacy ofMGN-3 equals or surpasses the very best immune-modulating drugs available but, in stark contrast to these, exhibits a complete lack of toxicity. (Copies of complete research papers and data on MGN-3 can be obtained from Lane Labs at 201-236-9090.)
Much ofthe data regarding MGN-3 has been previously published in technical journals and presented at international research conferences, but the information remains largely unknown to oncologists and other health professionals dealing directly with the cancer patient. The aim ofthis article is to bring this research to the attention of the practicing clinician, to summarize what is known about the actions of MGN-3, and explore its present role in the treatment of cancer patients.
Anti-viral activity: In addition to very encouraging results using MGN-3 in the treatment of malignancies, other research suggests a promising role for MGN-3 as a therapy for HIV, Hepatitis C, and other viral infections. MGN-3 has antiviral activity and also enhances the

body's immune response against virally­infected cells. In vitro research shows that MGN-3 inhibits replication of the HIV virus without cytotoxicity in a dose­dependent manner.' Human studies suggest that MGN-3 may also be extremely useful in the treatment of Hepatitis C. In these patients liver enzymes return to normal levels within 1-8 weeks of treatment with MGN-3. The results of our ongoing clinical research into the antiviral applications of MGN-3 will be the subject offuture reports.
The role of NK cells in the treatment of cancer
Over 150 different types of white blood cells have been identified and, of these, NK cells are one of the most common, representing up to 15% oftotal 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 to be the body's first line of defense against cancer and viral­infected cells.
Photo #1:
NK cell (top) attaching to a cancer cell.
Photo #2:
The cancer cell is dissolved and the NK cell moves on to another cancer cell.
TOWNSEND LETTER for DOCTORS & PATIENTS - JANUARY 2000
/

Circulating through the body by way of the blood and lymph systems, the majority ofNK cells present in the body are in a resting state. NK cells become more active in response to immunoregulatory proteins called cytokines. Once activated, the NK cells become quite rapacious in their search­and-destroy activities. Upon encountering a tumor cell, the activated NK cell attaches to the membrane ofthe cancer cell and injects cytoplasmic granules that quickly dissolve (lyse) the target cell. In less than five minutes, the cancer cell is dead and the NK moves on to its next victim. A single NK cell can destroy up to 27 cancer cells before it dies. Although quite small in comparison to tumor or virus cells, a single NK cell can often bind to two or more cancer cells at once.
The absolute number of NK cells present in the blood gives little indication of the efficiency of immune function. Instead, it is the activity ofthe NK cells - the avidity with which they recognize and bind to tumor cells - that is important. Most immuno-modulators, including MGN-3, do not increase the number or percentage of NK cells, but instead increase their level of activation. NK cell activity can be tested by means of a 4-hour radioactive-Chromium release assay. NK cells are isolated from a blood sample and are incubated in

vitro with a fixed number of chromium­labeled tumor cells. After 4 hours, the percentage of tumor cells that have been killed by the NK cells is determined, and this percentage can be used to describe NK cell activity.
In a healthy immuno-competent individual, when NK cell activity is examined at an effector:target ratio of 100:1, we would expect to see NK cell activity ranging from 60-75%. However, in cancer patients, NK cell activity typically ranges from near 0% to 30%. Although it is not entirely clear whether this is a cause or result of the disease process, there is evidence suggesting that low NK cell activity may be a risk factor for malignancy or metastases, as well as a negative prognostic indicator.' Therefore, agents that stimulate NK cell function are being sought as possible cancer therapeutic agents.
Proven human efficacy. We have previously presented data on 32 cancer patients, with different types of advanced malignancies.3.5 These patients had received and completed conventional therapy such as surgery, chemotherapy, radiation or hormonal therapy prior to participation in the study. The baseline NK cell activity was found to be low in all patients (10.8­49%). Oral ingestion ofMGN-3 at 45 mg! kg/day led to a significant increase in NK cell activity after only 1-2 weeks.

Cancer Immunology
The increase in baseline NK cell activity after two weeks of administration ranged from 145%-332% in breast cancer patients, 174%-385% in prostate cancer patients, 100%-240% in leukemia patients, and 100%-537% in multiple myeloma patients.
Longevity of response: One ofthe great and constant frustrations of the immunologist is the phenomenon of hyporesponsiveness. Science has identified many biological response modifiers (BRMs) that can substantially increase NK cell activity. However, the effect frequently attenuates over time, despite continued administration of the immunomodulator." One ofthe most exciting and distinguishing charac­teristics ofMGN-3 is that it appears to maintain its immunomodulatory effect over time. In long-term follow-up of our I patients (up to 5 years), we have observed that the enhancing effect of MGN-3 on NK cell activity is maintained indefinitely with continued administration.
Lack of toxicity: Another disappointment regarding synthetic immune boosters such as IL-2 and interferon is that these therapies, while variously effective in boosting the immune response against tumors and viruses, are exceedingly toxic and accompanied by numerous side effects, the most serious of which is kidney failure. By contrast, MGN-3 appears to be exceptionally non-toxic and well­tolerated.
In acute oral toxicity trials in rats, MGN-3 was found to be without toxic effects at dosages up to 36 g/kg. In addition, human trials using up to 45mg!


MGN-3
IL-2
MGN-3 + IL-2
TOWNSEND LETTER for DOCTORS & PATIENTS - JANUARY 2000


Cancer Immunology
>
kg/day of MGN-3 for six months have noted no abnormalities in blood chemistry or liver enzymes (SGOT and SGPT).'
Moreover, in 4 years of use with hundreds of patients, we have had no reports of side effects or interactions of any kind. In fact, our clinical experience suggests that MGN-3 can be safely and advantageously used in conjunction with conveptional treatment, including chemotherapy and radiation, both to increase the cytotoxic effect of the therapy and to decrease adverse side effects.
Clinical results: Enhanced
immune function is, however, only a theoretical victory if it does not lead to clinical improvement. But in fact, the documented increase in NK cell activity in cancer patients taking MGN-3 has been correlated to dramatic reductions in corresponding tumor markers and other pathology indicators, and, most importantly, to long-term stabilization or remission of disease in the large majority of cases (>85%). The complete clinical data for a total of 106 patients treated since 1995, including hematology and pathology reports, as well as incidence of remission and length of survival, are in the process of being collected and analyzed. It can be stated, however, that very few have been lost to follow up and virtually all continue to be in good health.
Discussion
Mechanisms of action: In addition to direct cytotoxic activity against tumor cells, activated NK cells also produce a variety of cytokines, including the interferons, interleukins, tumor necrotic factors and other growth factors. These cytokines, in turn, have direct antiviral and anti-cancer activities, as well as further immunomodulatory effects, such as upregulation of T- and B- cells, and further activation of NK cells. Our research suggests that MGN-3 works by simulating the body's natural production of interferon-y and tumor­necrosis factor-a.s These chemicals not only have direct anti-tumor activity themselves, but also directly and indirectly activate NK cell, B-cell and T-cells.
Synthetic cytokines interleukin-2 (IL-2), interferon-gamma (IFN-8) and tumor necrosis factor-alpha (TNF-a) have all been investigated as possible cancer-therapeutic agents, and have shown varying success. The most success has been seen with interleukin­2; however, the dosages needed to achieve positive results are associated with extreme toxicity.
MGN-3 may offer a novel solution to this dilemma. In vitro studies suggest that MGN-3 used in combination with low levels of IL-2 may significantly potentize the effect of IL-2. Figure 1 shows the effect on NK cell activity of
100

1 month Time after treatment
2 months
TOWNSEND LETTER for DOCTORS & PATIENTS - JANUARY 2000
MGN-3 and low doses ofIL-2, separately and in combination. The combined, synergistic effect of the two substances is significantly greater than either alone. This suggests that the immunomodulatory effect of low concentrations ofIL-2 on NK cell activity could be greatly augmented with the adjuvant use ofMGN-3.'
Clinical applications: Conven­tional medicine has excellent anti-tumor therapies that can significantly reduce the number of cancer cells. Unfortunately, we have seen that it is difficult to achieve a 100% kill rate without killing the patient in the process. At best, we can hope to kill 95­98% of the cancer cells with these therapies. At this point, a patient may be considered to be "in remission." Therapy is discontinued and the patient is closely monitored. However, as most oncologists are painfully aware, these remissions are frequently short-lived.
Most cytotoxic therapies are themselves immunosuppressive, lowering the activity of anti-cancer effector cells. Following chemotherapy or radiation, the few hardy cancer cells that survive the therapy are left to replicate largely unchallenged by a damaged immune system. When the cancer eventually resurfaces, it does so with increased ferocity and often with increased drug resistance.
In my opinion, the practice of watchful waiting wastes a golden opportunity to administer the coup de grace. At the very early stages of detection, or, in more advanced stages, when the tumor-load has been Feduced as far as possible by surgery and/or conservative cytotoxic therapies, boosting the immune system with biological response modifiers allows the body to eradicate the remaining cells that have escaped the chemicals, radiation, or surgeon.
However, MGN-3 cannot and should not replace debulking therapy, especially in the case of advanced malignancies. In these cases, even an extremely active immune response is easily overwhelmed by the huge numbers of cancer cells present. Instead, we recommend that cancer patients with solid tumors begin MGN-3 immunotherapy concurrent with or immediately following debulking
'.
!

Cancer Immunology
therapies. With this strategy we have the best chance of winning what essentially becomes a war of numbers.
In addition, we have found that cancers of the blood, such as leukemia and multiple myeloma, have been particularly responsive to MGN-3 therapy, presumably because the activated natural killer cells have even better access to these cancer cells than to those forming solid tumors.
MGN-3 can also be used to advantage as a preventive in high-risk populations. Unfortunately, the realities of our high-stress modern lifestyle, which include increasing exposure to mutagenic environmental toxins, the numbers of people who might be considered 'high-risk' are increasing. In one particularly disturbing study, researchers found persistently depressed NK cell activity in 14% of 'healthy' young adults.'o
Dosage considerations: As figure 2 illustrates, MGN-3 at 30 mglkg/day caused a steep (310%) increase in NK cell activity after only one week. NK cell activity continued to increase at a slower rate, to a peak activity of 500% over baseline by week 8 of this particular study, which involved 24 healthy subjects." This study also illustrates the interesting dose-dependent nature ofMGN-3. Lower doses (15 mglkg/day) yield a much slower initial increase, however all dosage levels achieve maximum activity by week 8. Within one month of cessation of treatment, NK cell activity returned to baseline. Clinical experience indicates that once maximum levels ofNK cell activity have been attained, they can in most <{ases be maintained indefinitely at the lower dosage level of 15 mglkg/day.
In the fight against cancer, time is of the essence. At the very early stages or immediately following debulking therapy, the numbers of cancer cells are relatively low and more susceptible to eradication by an aggressive immune system. Therefore, it is important to increase NK cell activity as quickly as possible in these patients. For these reasons, we recommend a loading dose of 30-45 mglkg/day for cancer patients. After two to three months, the dosage may be reduced to 15 mg/kg/day. In some individuals, the higher dose needs to be continued for a longer period of time.
Sustained clinical improvement (for example, normal tumor markers and negative imaging) is an indication that dosages can safely be reduced to a maintenance level. For general prevention, 15mg/kg/day is appropriate. The product is typically administered in 2-3 divided doses, accompanied by a meal.
Conclusion
Those involved with alternative and holistic medicine may be tempted to dismiss the introduction of yet another natural "immune booster" as hype. Many products are promoted to cancer patients on the strength of "scientific proof" of enhanced immune function. In most cases, however, the only research has been conducted in test tubes, or at most, in animals. But as many have noted, most recently apropos the work of Dr. Judah Folkman, if curing cancer in mice were equivalent to curing cancer in humans, this dread disease would already be a relic of a bygone era, rather than accompanying us into the new millennium.
Unlike most natural preparations, MGN-3 offers solid data collected from human clinical trials. This data offers compelling evidence that MGN-3 is a powerful biological response modifier that is free of toxicity or side effects. As such, it has enormous promise as an immunotherapy in the treatment of cancer and other diseases.
Correspondence:
Mamdooh Ghoneum, PhD Charles D. Drew University of Medicine and Science Department of Otolaryngology 1621 East 120th Street
Los Angeles, CA 90059 USA 323-563-5953
Fax 310-668-4554
References
Ghoneum, M, Anti-HIV activity in vitro of MGN-3, an activated Arabinoxylane from rice bran, Biochemical Research Communi­cations 1998, 243:25-29.
Whiteside T, Herberman, R, Human Natural Killer Cells in Health and Disease, Clinical Immuno­therapeutics 1994, 1(1):56-66.
Ghoneum, M, Manatalla, G, NK immunomodulatory function in 27 p2.tients by MGN-3, a modified ara­binoxylane from rice bran, Abstract, 87th Annual Meeting of the American Association for Cancer Research, April, 1996, Washington, DC.
Ghoneum, M, Immunomodulatory and Anti-cancer properties of MGN-3, a modified xylose from rice bran, in 5 patients with breast cancer, Abstract, American Association for Cancer Research Special Conference:
The Interface between basic and applied research. November, 1995, Baltimore, MD.
Ghoneum, M, NK
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