Immunomodulation of Traditional Chinese Medicines: Applications and Implications for Cancer Medicine

As cancer continues to be one of the leading causes of death in Australia and worldwide, with an ageing population it is likely that malignancy will continue to be a major health problem affecting a significantly greater portion of the population. Therefore there is an ongoing need for the development of novel therapeutic treatment options including anti-cancer compounds and immunotherapies to improve the health outcomes of people living with cancer. Natural products such as medicinal plants are a vital source of novel drugs and advantageous because they offer unmatched chemical diversity with structural complexity and biological potency. Traditional Chinese Medicines (TCM) have been the subject of much research and are commonly employed as adjuvants to cancer treatment regimens due to their ability to confer protective, toxicity reducing and immunomodulatory effects. In particular, mushroom derivatives have been well studied and have been identified to possess immunomodulatory effects, but clear evidence of their ability to augment immunological responses against specific antigens is slowly emerging. Polysaccharides and glycoproteins in particular are thought to be the active constituents present in these mushrooms and in many Chinese herbs such as Astragalus membranaceus, Ligustrum lucidum, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa and Panax ginseng. This thesis seeks to investigate the application of glycoprotein based herbal medicines such as Coriolus vericolor, Astragalus membranaceus and Ligustrum lucidum in the cancer context to modulate the immune response in vitro, in vivo and clinically

Schematic diagram of the events that give rise to cognate interactions between T-cell and B-cells.

<p>Schematic diagram of the events that give rise to cognate interactions between T-cell and B-cells.</p

a-f. PSP significantly increase NP-specific IgG responses compared to the vehicle control.

<p>Expression of the total high affinity and low affinity NP-specific IgG titers were measured from two-fold serially diluted serum samples (from 1/40-1/80 for day 4 to 1/8000-1/10000 for day 10 onwards) using NP₂-per BSA (NP₂) and NP₁₈-per BSA (NP₁₈) respectively by ELISA. The low affinity NP-specific IgG antibody responses to ACACIA were significant at day 4 but at no other time point (day 7, 10, 14 or 21) compared to PSP. The ratio between the expression of total high affinity and low affinity NP-specific IgG responses was significant for ACACIA at day 4 compared to PSP. NP₂ baseline very low (data not shown). Data are shown as the median from two independent experiments with 5–6 mice per group. *P < 0.05.</p

Schedule for acclimatization, immunization, PSP treatment and sacrifice of mice.

<p>5 week old mice were allowed to acclimatize for one week, immunized with NP₂₅-CGG at 6 weeks, groups of mice were then gavaged daily with PSP, ACACIA or MQ for up to 21 days and sacrificed at various time points (days 0, 4, 7, 10, 14 and 21).</p

a-f. PSP significantly decreased NP-specific IgM responses at days 4 and 21 compared to ACACIA.

<p>C57BL/6 mice were immunised with NP₂₅CGG and serum was collected on days 0, 4, 7, 10, 14 and 21. NP-specific IgM titers were measured from two-fold serially diluted (1/40-1/80) serum samples by ELISA. ACACIA significantly increased NP–specific IgM responses at day 21 compared to NP-CGG alone. Data are shown as the median from two independent experiments with 5–6 mice per group. *P < 0.05.</p

a-d. Absence of any significant NP- specific IgA responses to PSP or ACACIA.

<p>After NP-CGG immunization no changes in IgA antibody responses were observed at any time point (day 0, 10, 14 or 21) to PSP or ACACIA. NP- specific IgA titers were measured from two-fold serially diluted (1/50-1/100) serum samples by ELISA. Data are shown as the median from two independent experiments with 5–6 mice per group.</p