glucan projects

 

To summarize use of glucan in tumor therapy:

To summarize use of glucan in tumor therapy:

  • Success requires anti-tumor antibody that generates iC3b on tumors
  • Patients with breast cancer generate antibody response and will respond to glucan alone as long the tumors are targeted with antibody and iC3
  • Humanized antibodies such as Herceptin and Rituximad are good targets for combined therapy with glucan
  • Even tumors that have lost MHC class I might be targets
  • May function to reduce myelosuppression caused by chemo- or radiation therapy
Basic characteristics:

B1,3-Glucans can be isolated from numerous sources including almost every species of yeast. However, b1,3-glucan derived from Saccharomyces cerevisiae (baker’s yeast) has been the most extensively studied and the highest biological effects have been shown. b1,3-Glucan forms a significant part of the yeast cell wall, together with mannan, proteins, lipids and small amounts of chitin. In addition to yeast, b1,3-glucans can be isolated from bacteria, mushrooms, algae or cereal grains. The structure of the b1,3-glucan depends on both source and the type of isolation.  Different physicochemical parameters, such as solubility, primary structure, molecular weight or branching play a role in biological activities of glucans.

Polysaccharides have a long history as immunomodulators. The first investigations of the so-called Shear’s polysaccharide were published almost 60 years ago. When pharmacological actions of glucan are concerned, it all started with zymosan, which is basically a crude version of glucan. In 1956 it has been found that zymosan increased resistance to E. coli, later that it promotes rejection of sarcoma. Later was shown that soluble glucans from mushrooms trigger rejection of sarcomas, in 1978 happened British trials of particulate glucan injected in breast tumors. In 1983 Japanese approved clinical use of Lentinan and Schizophyllan in patients with gastric carcinoma.

How does glucan work?

However, the important effects of glucan do not end in activation of immunocytes. Besides the ability to stimulate the cells of the immune system to perform optimally and maximally, beta glucan also “cares” about their numbers. It is well established that all cells involved in immune reactions originate from common precursors – stem cells originating from bone marrow. The influx of new cells from bone marrow is steady throughout or entire life. The formation and migration of newly formed immunocytes is limited, and here again, beta glucan comes to the rescue. It stimulates the production of precursor cells in bone marrow, resulting in a more rapid flow of new immunocytes into the bloodstream and into the various lymphoid organs throughout the body. These effects are important not only under normal conditions, as the increased amount of immunocytes in circulation means increased surveillance against potential invaders, but particularly in case of extreme stress such as in cancer, where the limited influx is further reduced by exhaustion of the immune system and by treatments such as irradiation and chemotherapy.

This effect alone would be enough to consider beta glucan one of the most significant anti-cancerous immunostimulants we know, but beta glucan has still another ace up its sleeve. In addition to the already mentioned specific stimulation of cell surface receptors, beta glucan is able to nonspecifically activate of the immune system via the release of biologically important molecules. Upon entering the blood stream, beta glucan activates various cells of the body to release numerous biological factors and signals molecules known to influence our defensive systems. Among these factors are: tumor necrosis factor (TNF), interleukins 1 and 6, hydrogen peroxide, and gamma interferon, all of which are proven effective in our fight against cancers and other invading microorganisms. These effects are systemic, which means that even after localized application of glucan, these immunoactive molecules can influence the activity of immune system throughout the entire human body. In addition to the direct effects on tumor cells, the synthesis and release of these signals has also a direct impact on macrophages and T lymphocytes capable of producing other cytokines. In this nonspecific way, beta glucan helps to boost defensive reactions by triggering the whole complicated cascade of events leading to a fully armed immune system.

Position of glucan in evolution:

Original studies on the effects of b1,3-glucan on the immune system focused on mice. Subsequent studies demonstrated that b1,3-glucan has strong immunostimulating activity in wide variety of other species, including earthworms, shrimps, fish, chicken, rats, rabbits, guinea pigs, sheep, pigs, cattle and humans. Based on these results it has been concluded that b1,3-glucan represents a type of immunostimulant that is active across the evolutionary spectrum, likely representing an evolutionarily conserved innate immune response directed against fungal pathogens.

receptor:

NK cell CR3 receptor (CD11b/CD18) has been found to mediate specific killing of tumor cells coated with C3 fragment of complement. Our experiments demonstrated that soluble glucan (isolated and purified from yeast) can activate NK cell CR3 receptor to bind to C3-coated targets and to mediate specific lysis of these target cells. Many published reports and our own investigation have shown that many tumors may be naturally targeted for killing by NK cells, whose CR3 receptors had been activated to trigger cytotoxicity by glucan. Glucan injected in vivo into mice with established human breast tumor cells was able to suppress the tumor growth up to 80% after only two weeks of treatment. The major goal of this project is to optimize the actions of glucan in specific killing of breast cancer cells and to prepare glucan with the highest activation effects.

commercial use of glucan

 

       HUMANS

 

 

  • Success requires anti-tumor antibody that generates iC3b on tumorss
  • Patients with breast cancer generate antibody response and will respond to glucan alone as long the tumors are targeted with antibody and iC3
  • Humanized antibodies such as Herceptin and Rituximad are good targets for combined therapy with glucan
  • Even tumors that have lost MHC class I might be targets
  • May function to reduce myelosuppression caused by chemo- or radiation therapy

1
   animals

 

 

  • Success requires anti-tumor antibody that generates iC3b on tumorss
  • Patients with breast cancer generate antibody response and will respond to glucan alone as long the tumors are targeted with antibody and iC3
  • Humanized antibodies such as Herceptin and Rituximad are good targets for combined therapy with glucan
  • Even tumors that have lost MHC class I might be targets
  • May function to reduce myelosuppression caused by chemo- or radiation therapy

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