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 immunornodulatory function was examined in 27 cancer patients. MGN3 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 myeloma (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:
1) Patients had low level of basal NK activity (10.8-40%),
2) 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%,
3) Enhancement of NK activity continues to rise at 3 and 6 months after treatment.
We concluded that the high augmentory effect of MGN-3 makes it a promising immuno-therapeutic agent for treatment of cancer.
ENHANCEMENT OF HUMAN NATURAL KILLER CELL ACTIVITY
BY MODIFIED ARABINOXYLANE FROM RICE BRAN (MGN-3)
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 51 CR-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 calls at all concentrations used. In a dose-dependent manner, MGN-3 at 15 mg/kg/day increased natural killer activity after 1 month posttreatment (two-fold over control value), while significant induction of natural killer activity at 30 mg/kg/day was detected as early as 1 week posttreatment (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 againt 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 to 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 CD56+ 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 251 00 pg/mL. Thus, MGN-3 seems to set 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.
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 ConferenceAugust I5-16, 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 IL-2 (rIL-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 rIL-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),. rIL-2 alone (500u/ml) and MGN-3 (l mg/ml) plus rIL-2 (500u/ml). Results showed that MGN-3 and rIL-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 rIL-2 (332.7% of control). The mechansm underlying this phenomenon is not fully understood but could be attributed to action of MGN-3 on TNF-Alpha production. Results showed that TNF-Alpha levels from control untreated PBL of 20 subjects was 195 pg/ml +/- 102. Treatment with rIL2 showed no change in TNF-alpha level (216ng/ml +/- 100), while MG-3 significantly increased TNF-alpha production (5773pg,/ml +/- 2653). On the other hand, a synergistic effect of MGN-3 plus rIL-2 resulted in a further increase of TNF-alpha production (8127 pg/ml +/- 2587). We conclude that: 1) MGN-3 is a potent TNF-alpha producer, and 2) the immunomodulatory function by low concentration of rIL-2 on anti-tumor activity by NK cells could be greatly augmented by the concomitant use of MGN-3.
ANTI-HIV ACTIVITY IN VITRO OF MGN-3,
AN ACTIVATED ARABINOXYLANE FROM RICE BRAN
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 hyphomycotes mycelia, was tested for anti-HIV activity in vitro. MGN-3 activity against HIV I (SF strain) was examined in primary cultures of peripheral blood mononuclear cells. MGN-3 inhibited HIV-1 replication by: (1) inhibition of HIV-1 p24 antigen production in a dose dependent manner; MGN-3 at concentrations of 12.5, 25, 50 and 100 ug/L 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.
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