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Monoclonal Antibodies Study Results

A Simple Matter of Biology

A couple of decades ago cancer was almost purely a generalized cytotoxic phenomenon, non unlike destroying an entire town in order to flatten just a single building. Everyone wished there was a means to target just the cancer cells without decimating the cancer patient's entire body along with it. Using our body's immune system-already adept at selective killing-was an obvious choice. However, since cancer patients often have poor immune systems, some sort of outside help from newer cancer therapies was necessary.

Today, immune-related cancer research is the driving force behind the latest developments in the medical sceince. Many positive strides toward selectively destroying cancer cells have been made. Many "chemotherapy" treatments used today are actually immune-boosting therapies directed at cancer cells. Surprisingly, some immune-enhancing protocols, like those using beta-1,3-glucan (or beta-glucan), a polysaccharide isolated from fungal sources like Baker's yeast, did not have to be created from scratch in a laboratory. Apparently, nature had the answer for us all along.

Beta glucan has been studied extensively by scientists and has been found to be effective in the treatment of cancers as diverse as prostate cancer and lymphoma. Gradually, the mechanism of action behind the anti-cancer activity of beta-glucan has been uncovered, giving scientists and patients alike the confidence to trust the anti-cancer effects of beta-glucan in many clinical situations.

A comprehensive article on beta-1,3-glucan's anti-tumor properties was published by Feng Hong, et al., in The Journal of Immunology (J Immunol 2004;173:797-806). The authors of the article have addressed the tough, yet vital, questions about how beta-glucan enters the body, arrives to the key immune areas of the body and is effective in aiding in tumor cell death.

For example, a few older studies on the anti-tumor effects of beta-glucan used the intravenous form of beta-glucan because it was believed that the beta-glucan molecule was too big to be absorbed by the intestinal tract if given orally. The research backing up the current article, however, clearly shows that beta-glucan given orally is just as effective as the intravenous route. Using fluorescein-stained beta-glucan, it was found that the molecule is picked up by intestinal macrophages and is carried to sites such as the lymph nodes, the spleen and the bone marrow-all sites of intense immune activity. (See figure 1).

macrophage engulfed beta glucan particulates

The study also revealed that, once inside the macrophage cells, beta-glucan is broken down into smaller fragments, which are then secreted. As smaller pieces, the beta-glucan is picked up by an important receptor site, called C3, on neutrophils and on other cell types that destroy cancer cells. The C3 receptor is absolutely essential for the ability of neutrophils to be effective as cancer-killers.

Figure (1), (2) and (3) shows clearly that the macrophage cells do, indeed, take up the stained beta-glucan and that the neutrophils later bind to the smaller molecules at sites where tumor cells are destroyed.

macrophage engulfed beta glucan particulates marrow

As it turns out, the C3 receptor on neutrophils requires the dual attachment of beta-glucan and a protein called iC3b that is conveniently attached to the tumor cell by anti-tumor antibodies and the human complement system. Once both are attached, the tumor cell can be destroyed. If beta-glucan is missing, tumor cell death is poorly accomplished. Similarly, if beta-glucan is used alone without anti-tumor antibodies putting the iC3b protein marker on the cancer cell, not much happens either.

macrophage engulfed beta glucan particulates

Our body actually makes some anti-tumor antibodies on its own but, for maximal effect, giving both beta-glucan and a source of anti-tumor antibodies seems important in the treatment protocols involving patients with an already active cancer. The anti-tumor antibodies "prime" the tumor cells with the iC3b protein so that, along with beta-glucan, the C3 receptor on neutrophils is completely covered.

Figure (4) shows what is involved in completing the C3 receptor binding that triggers tumor cell death.

neutrophil cancer tumor beta glucan

Experimental models involving mice were done in Dr. Hong's study that showed how tumor growth was not suppressed in mice injected with tumor cells if given only anti-tumor antibody without the added effect of beta-glucan. If both beta-glucan and anti-tumor antibodies were given, both tumor size and mortality rate were significantly improved.

The authors also concluded that either oral or injected beta-glucan were effective.

Figure (5) shows the effect on overall mortality in mice with cancer given beta-glucan as part of the anti-cancer protocol.

antibodies_beta_glucan

Several immunotherapy agents (e.g. Rituximab, Cetuximab and Traztuzumab), while sounding a lot like traditional chemotherapy medications, are actually the anti-tumor antibody products needed to work with beta-glucan to provide superior immuno-destruction to selected tumor cells.

Many other research studies have concluded that beta-glucan aids in tumor cell death; however, the study just outlined was the first to prove that oral beta-glucan is as effective as the intravenous product. It was also the first to clearly demonstrate exactly why beta-glucan is as effective as it appears to be in clinical studies.

Thanks to modern scientific studies involving cancer therapy provided in ways greatly different from that used even 10-15 years ago, including those addressing the positive adjunctive use of beta-glucan, the deleterious side effects of cancer treatment have lessened and the survival rates from cancer are better than ever.

[1] Hong F. Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J Immunol. 2004;173:797-806.