Abstract 3515: Maitake D-Fraction, a natural mushroom extract, synergizes with Interleukin-2 for increased lytic activity of peripheral blood mononuclear cells against various human tumor cell histologies
Authors: Johnson Derek M. , Edwards Eliot , Rosales Adriana , Birdsall Timothy C. , Staren Edgar D. , Braun Donald P. 
Published: August 2012

Abstract
Maitake (Grifola frondosa) has been recognized by naturopathic physicians as a medicinal mushroom capable of immune support. Maitake D-Fraction (MDF), a component of the maitake mushroom isolated during hot-water extraction, is rich in α-Glucans and commonly prescribed as a dietary supplement. Because MDF is widely available and easily tolerated, it is highly desirable for the cancer patient looking for immune support via natural products. Previous research has suggested that a dietary MDF regimen can enhance immune function in humans. However, studies to investigate the capacity of MDF to increase tumor immunity are lacking. This study was designed to investigate whether human peripheral blood mononuclear cells (PBMC) treated with MDF develop increased cytolytic capacity against human tumor cells. Cytolysis mediated by MDF-activated PBMC was compared to that of naïve PBMC (media control) and PBMC that were treated with interleukin-2 (IL-2). Immune mediated tumor cytolysis was assessed used a standard Chromium-Release Assay and expressed as number of lytic units (LU)/10^7 effector cells. Target cells for the assays included the PANC1 pancreatic cancer cell line (PA) purchased from ATCC, and single cell suspensions created from peritoneal carcinomatosis (PC) and renal cell carcinoma (RC) tumors resected from patients. Against the PA cells, the LU observed were 16.9 (media control), 12.9 (1ug/ml MDF), 23.8 (10ug/ml MDF) and 28.9 (100ug/ml MDF). The corresponding LU values against PC cells were 7.6, –13.4, –14.2, and –12.1, respectively, and against RC cells 12.3, 2.7, 2.0, and 8.2, respectively. Predictably, PBMC stimulated with an optimally activating dose of IL2 (200U/ml) exhibited a marked increase in LU against all target cells. Nevertheless, when PBMC were stimulated concurrently with both IL-2 and MDF activation was increased further. Thus, LU against PA target cells were 73.0 for PBMC treated with IL-2 alone, and 110.6 for PBMC treated with IL-2 plus 100ug/ml MDF. The corresponding LU values against PC target cells were 37.1 (IL-2 alone), and 66.4 (IL-2 plus 100ug/ml MDF) and against RC target were 94.0 (IL-2 alone) and 110.7 (IL-2 plus 100ug/ml MDF). This study shows that MDF has the capacity to increase the lytic activity produced by an optimally activating dose of IL-2, eliciting greater killing of a variety of human cancer cells than what can be achieved with IL2 alone. It is reasonable to assume that MDF can elicit a similar effect at lower doses of IL-2. Given the toxicity of IL-2 observed in humans, the potential to elicit the desired immune stimulation by combining lower doses of IL-2 with MDF becomes highly desirable. Future clinical trials should be designed to investigate the ability of MDF to elicit optimal immune stimulation with more tolerable doses and schedules of IL-2.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3515. doi:1538-7445.AM2012-3515