The potential of cancer therapies about to mushroom

Hiratake and Shiitaki mushrooms have long held a position in oriental cuisine, however recent work by Dr Ross, of the University of Louisville in Kentucky has now shown how beta-glucan, an extract from these mushrooms can also be harnessed for its cancer fighting properties.
Over the past 15 years mushroom extracts have been tested in patients with various forms of cancer with promising albeit, variable results. In a report published today by the pharmaceutical consultants, LeadDiscovery, it is described how Dr Ross has elucidated the mechanism by which beta-glucan works, and how this class of drugs can now be harnessed to drive forward our fight against cancer.
The key to beta-glucan's effect is its ability to interact with the complement pathway, a cascade of naturally occurring chemicals that make up an important part of the bodies immune system. Once antibodies bind to the surface of invading micro-organisms, they activate the complement pathway with one particular component, the iC3b fragment of the serum complement protein C3 coating the microbe. This then causes binding to immune cells via surface receptors. One good example of this mechanism occurs in response to yeast infections. In early experiments, Dr Ross showed that leukocyte activation depended on the simultaneous binding of yeast beta-glucan to the iC3b receptor.
Dr Ross, who also holds a position at the James Graham Brown Cancer Center, has since shown how this mechanism can be used to fight cancer. The body naturally produces antibodies that can bind cancerous cells activating the complement system. In ground breaking studies in 1996, Dr Ross focussed on YAC-1 cells, a cancerous cell type derived from mice. Human immune cells were forced to recognize YAC-1 cells by coating them with human iC3b. If small quantities of soluble beta-glucan were added to the immune cells, they were then able to kill the majority of the cancerous cells.
Further studies were performed in mice with mammary tumors. Mice normally produce antibodies that can recognize this type of tumor, allowing immune cell recognition. Irrespective, mice still rapidly succumbed to tumor progression unless treated with small quantities of beta-glucan which caused tumors to shrink by over 90% within 2 weeks. Likewise, in freshly excised human mammary tumors coated with antibodies and also iC3b, immune cells were able to dramatically attack the cancerous cells if they were first primed with beta-glucan. This was dependent on tumor cells being coated with antibodies and although this sometime occurs naturally, it is by no means a consistent phenomenon explaining why early clinical trials assessing mushroom extracts yielded variable results.
The work of Dr Ross has led to the understanding of beta-glucan and this class of drugs can at last be exploited. One particularly exciting prospect is the use of beta-glucan alongside new antibody and vaccine treatments. According to LeadDiscovery "well over 30 companies are involved in the development of antibodies targeted towards oncology" however as Dr Ross states "It is widely accepted in the field of tumor immunotherapy that antibodies are usually ineffective in killing tumors, and that effective immune destruction of cancer requires the development of cytotoxic T cells that recognize tumor-specific antigen peptides presented on cell surface major histocompatibility complex (MHC) class I molecules." This usually fails during cancer progression and the effectiveness of antibody therapy as well as cancer vaccines, which are a focus of almost 100 companies should be dramatically enhanced if patients are first primed with beta-glucan-like molecules.
So what are the next steps. Dr Ross has developed a recombinant fragment the iC3b receptor that binds of beta-glucan and this offers a useful tool to companies involved in high throughput screening, who wish to identify molecules with act like beta-glucan but with even greater effectiveness. Alternatively computer modeling is rapidly growing as a tool for the pharmaceutical industry and by using beta-glucan as a scaffold improved drugs can be designed. The work of Dr Ross offers exciting breakthroughs. According to a spokesperson from LeadDiscovery "beta-glucan has been shown to be safe in clinical trials and now Dr Ross's work shows that when used along-side cancer vaccines and antibodies, a highly specific and effective anti-cancer effect should be reached. The development of beta-glucan mimics should help revolutionize the treatment of cancer and we wait with excitement for the commercialization of these advances".
For further information contact Dr Ross at gordon.ross@louiville.edu or access "beta-glucan, a candidate for cancer immunotherapeutics" through the LeadDiscovery website at www.leaddiscovery.co.uk