From Bench to Bedside: The Growing Use of Arabinoxylan Rice Bran (MGN-3/Biobran) in Cancer Immunotherapy

Review Article

Austin Immunol. 2016; 1(2): 1006.

From Bench to Bedside: The Growing Use of Arabinoxylan Rice Bran (MGN-3/Biobran) in Cancer Immunotherapy

Ghoneum M*

Department of Otolaryngology, Charles Drew University of Medicine and Science, USA

*Corresponding author: Mamdooh Ghoneum, Charles Drew University of Medicine and Science, Department of Otolaryngology, 1621 E. 120th Street, Los Angeles, California 90059, USA

Received: July 25, 2016; Accepted: August 23, 2016; Published: August 26, 2016


MGN-3/Biobran is a denatured hemicellulose obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from Shiitake mushrooms. Over the last 24 years, our fundamental research objective has been to study the biotherapeutic activity of MGN-3 as a treatment for cancer based on its ability to activate the immune system. This objective has been pursued in vitro, and in animal and human studies. This review is focused on the immunomodulatory effects of MGN-3 and on its potential as an anticancer agent. In vitro studies showed that culturing different human and murine cancer cell lines with MGN-3 resulted in a reduction of the survival rate of cancer cells. In vivo studies have also shown that MGN-3 induces tumor regression in several models of animal bearing tumor, including gastric cancer, neuroblastoma, and Ehrlich carcinoma. In addition, the anti-cancer activity of MGN-3 has been shown in human clinical trials and in several case reports on patients with Hepatocellular Carcinoma (HCC) and progressive and partially metastasized cancer. Patients that were treated with MGN-3 in addition to Conventional Therapy (CT), as compared with CT alone, showed: 1) less recurrence of cancer, 2) higher survival rate and 3) improved Quality of Life (QOL) as characterized by improvements in physical activity, appetite, sleep, and digestion, and a decrease in pain and anxiety.

This review summarizes the preclinical and clinical research on MGN-3/ Biobran since it was first patented in 1992. Various animal studies and human clinical trials including different types of malignancies have demonstrated that MGN-3 is a potent Biological Response Modifier (BRM). MGN-3 enhances the cytotoxic reactivity of immune cells with anti-cancer activity such as NK and CD8+ T cells via increasing cell granularity, stimulates the production of interferons, IL-2 and IL-12, and functions as a natural adjuvant for Dendritic Cells (DC). Therefore, MGN-3 may be used in DC-based vaccine strategies against infections and cancer. Importantly, MGN-3 is a unique BRM because it is a safe non-toxic agent and does not exhibit hyporesponsiveness. MGN- 3 has the potential to be a novel and promising immune modulatory adjuvant that could complement the existing immunotherapeutic modalities for cancer patients.

Keywords: Biobran; Arabinoxylan; Natural Killer cells; Dendritic cell; BRM


Despite the last decade of advances in treatment options, cancer remains the second leading cause of death in the United States [1]. Unfortunately the outcome of standard cancer treatments is often poor due to the emergence of Multidrug Resistance (MDR) during the course of treatment. MDR cells are a significant factor in the failure of chemotherapeutics as evidenced by high relapse rates for the majority of patients [2,3]. Therefore, to increase cancer survival and improve symptom control, there is a strong need for new and better approaches to cancer treatment. Today, the National Cancer Institute (NCI) has acknowledged the importance of immune therapy for the treatment of cancer. NCI, other health organizations, and professionals in the field of oncology are currently working to harness the immune system to fight cancer and to expand immunotherapy in combination with other types of cancer treatment, such as targeted therapy, chemotherapy, and radiation therapy.

The field of cancer immunotherapy has recently received increasing interest as a promising approach to tackle cancer. This approach involves fighting off cancer cells by using the patient’s own immune system. The theory of immune surveillance postulates that immune effectors can recognize and destroy spontaneously arising malignant tumor cells. Tumors may develop when transformed cells escape the immunologic host defense mechanism [4-6]. With respect to immunotherapy, Biological Response Modifiers (BRM) are designed to activate the host immune response to destroy cancer cells. Several BRMs of fungal and bacterial origin have been developed, but most of these BRMs have been associated with severe side effects and exhibit hyporesponsiveness. MGN-3/Biobran, an arabinoxylan from rice bran, is a notable BRM that possesses the two important characteristics of a successful BRM: 1) safe, non/minimal toxicity [7- 12] and 2) does not exhibit hyporesponsiveness [13,14].

Bran and fiber can provide health benefits of cancer risk reduction [15], including reduction on the growth of colorectal cancer cells [16] and the number of intestinal adenomas in mice [17]. Further studies have been focused on the anti-cancer activity of rice bran extracts and products derived from them [18,19], such as IP6 [20], and several phytosterols and triterpenoids [21]. The current review describes rigorous bench research on MGN-3/Biobran over the last 24 years. The research shows its translational potential as a novel adjuvant for the treatment of cancer by demonstrating its anti-cancer activity and the mechanisms underlying its effect. The treatment potential of MGN-3 is exemplified through animal studies and human clinical trials on patients with different types of malignancies, including a 3-year randomized clinical trial of the anti-cancer activity of MGN-3 against Hepatocellular Carcinoma (HCC) [22].

The mechanisms by which MGN-3 exerts its anti-cancer activity involve chemotherapy sensitization and immune modulation. The chemosensitizing effect of MGN-3 has previously been reviewed in [18]. Therefore, in this review we focus on the immune modulatory effect of MGN-3 as manifested by its ability to activate different arms of the immune system such as NK cells [9,13,23-26] and DCs [27-29], and modulation of the production of cytokines such as interferons [9,23,28,29], IL-2 and IL-12 [25,28]. This research review shows that MGN-3 has translational potential as a novel immune modulatory adjuvant for the treatment of cancer. Further studies are needed in multiple clinical trials.

Preclinical research

Preclinical research on the anti-cancer effects by MGN-3 has been examined. MGN-3 is a denatured hemicellulose obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from Shiitake mushrooms [30]. The main chemical structure of MGN-3 is an arabinoxylan with a xylose in its main chain and an arabinose polymer in its side chain (Figure 1). Earlier studies have shown reduction in the survival of different human and murine cancer cell lines post cultures with MGN-3. In a dose- and time-dependent manner, MGN-3 reduced the survival rate of human Breast Cancer Cells (BCC) MCF-7 and ZR-75-1, murine metastatic BCC 4T1 [31-33], and human multiple myeloma cell line U266 [34].