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					Understanding cancer immunology for herbal research in cancer

施文远博士 Dr. Daniel Man-yuen SZE
1

Hong Kong Polytechnic University 2 Australian Collaborative Centre in TCM

Cancer immunology
1. Novel anti-cancer TCM-related cytotoxic compounds (Endophytes) 2. Natural anti-cancer T-cell immunity 3. Defective blood dendritic cells in cancer 4. TCM targeting Cancer Stem Cells

TCM herbs as sources of endophytes and anti-cancer compounds
By Kristin Miller
Supervisor Dr Daniel Sze

background

Yew Trees

Screen TCM herbs for the presence of endophytes that have the potential to produce bioactive substances
Bacterial and Fungal DNA PCR to amplify fungal and bacterial genes Plant DNA (NOT PLANT GENES)

Bands of amplified DNA Identify plants which contain endophytes producing bioactives

Identify plant samples positive for NRPS, PKS and Taxol biosynthetic genes

Cancer immunology
1. Novel anti-cancer TCM-related cytotoxic compounds (Endophytes) 2. Natural anti-cancer T-cell immunity 3. Defective blood dendritic cells in cancer 4. TCM targeting Cancer Stem Cells

Naturally Occurring Clinically Significant Anti-Cancer (Multiple Myeloma) Cytotoxic T cell Expansions

Multiple Myeloma

Pre Transplant
30

% of CD3 cells

20

T cell Expansions if >3SD of aged-matched controls.

10

0
1 2 3 5.1 5.2 5.3 7.1 8 9 11 12 13.1 13.614 16 17 18 20 21 22 23

TCR Vβ repertoire

After 8 months thalomide
30

% of CD3 cells

20

10

0
1 2 3 5.1 5.2 5.3 7.1 8 9 11 12 13.1 13.614 16 17 18 20 21 22 23

TCRVβ repertoire

Cancer immunology
1. Novel anti-cancer TCM-related cytotoxic compounds (Endophytes) 2. Natural anti-cancer T-cell immunity 3. Defective blood dendritic cells in cancer 4. TCM targeting Cancer Stem Cells

Progression Free Survival 多发性骨髓瘤中特异性CD8+T细胞 與 ALLG- MM6 Thalidomide 沙利竇邁的臨床試驗
1.0

中位存活率
Thal and T cells Thal and No Tcells No Thal and T cells No Thal and No T cells χ2= 9.5; p=0.002

Progression free

0.5

0.0 0 10 20 30 40 50 60

Sze et al, Blood 2001; Sze et al, Leuk Lymphoma 2003;

Months Median Survival Thal and T cells Thal and No T cells No Thal and Tcells No Thal and No T cells

40.1 months 28.3 months 21.3 months 15.9 months

Effective anti-cancer multi-directional mechanisms

多向抗癌機理 Thalidomide
抗氧化 Anti-oxidant 抗 转移 Anti-metastasis

沙利竇邁
免疫調節
Immunomodulation

微環境調節 microenvironment
modulation

殺滅腫瘤 Anti-tumour

抑制血管新生 Anti-angiogenesis
Bruno et al (2004) Lancet Oncol 5:430 Sze et al (2006) Current Cancer Drug Targets. 6: 89

To kill Tumor cells

To promote Anti-cancer T/NK cell activities

Do selected (Chinese) herbal medicines exhibit this desirable differential cytotoxicty towards cancer cells versus normal cells (heart, liver, kidney, nerve, bone) including peripheral blood mononuclear cells (PBMCs)?
Tan, A. & Sze, D.M. (2008) Indigenous herbs and Cancer. Journal of Complementary Medicine. 7, 48. High-throughput screening platform for anticancer therapeutic drug cytotoxicity. Sekhon BK, Roubin RH, Tan A, Chan WK, Sze DM. Assay Drug Dev Technol. 2008 Oct;6(5):711-22.

Cancer immunology
1. Novel anti-cancer TCM-related cytotoxic compounds (Endophytes) 2. Natural anti-cancer T-cell immunity 3. Defective blood dendritic cells in cancer 4. TCM targeting Cancer Stem Cells

Defective Dendritic cells in cancer can be corrected by Interferon-γ and IL-12 active
TGFβ latent TGFβ IL-10
Immature DC Malignant Plasma cell

Dysfunctional Dendritic cells

NORMAL
T cell Immature DC

Mature DC = CD80


				
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