Tocotrienols are good adjuvants for developing cancer vaccines

被引:22
作者
Hafid, Sitti Rahma Abdul [1 ,2 ]
Radhakrishnan, Ammu Kutty [2 ]
Nesaretnam, Kalanithi [1 ]
机构
[1] 6 Persiaran Inst, Malaysian Palm Oil Board, Bandar Baru Bangi 43000, Selangor, Malaysia
[2] Int Med Univ, Fac Med & Hlth, Div Pathol, Kuala Lumpur 57000, Malaysia
关键词
DENDRITIC CELLS; PALM OIL; TOCOPHERYL SUCCINATE; ESTABLISHED TUMORS; GENE-EXPRESSION; RICH FRACTION; GROWTH; VACCINATION; APOPTOSIS; INHIBIT;
D O I
10.1186/1471-2407-10-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Background: Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods: In this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil ( control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results: Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-gamma and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion: Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.
引用
收藏
页数:10
相关论文
共 29 条
[1]
Abbas AK., Basic Immunology functions and disorders of the Immune system, VFourth
[2]
APRASAD KN, 2003, J AM COLL NUTR, V22, P108
[3]
Cutting edge: Rapid in vivo killing by memory CD8 T cells [J].
Barber, DL ;
Wherry, EJ ;
Ahmed, R .
JOURNAL OF IMMUNOLOGY, 2003, 171 (01) :27-31
[4]
Presentation of exogenous protein antigens on major histocompatability complex class I molecules by dendritic cells: Pathway of presentation and regulation by cytokines [J].
Brossart, P ;
Bevan, MJ .
BLOOD, 1997, 90 (04) :1594-1599
[5]
Candido KA, 2001, CANCER RES, V61, P228
[6]
Bacterial probiotic modulation of dendritic cells [J].
Drakes, M ;
Blanchard, T ;
Czinn, S .
INFECTION AND IMMUNITY, 2004, 72 (06) :3299-3309
[7]
FIELD RC, 1998, P NATL ACAD SCI USA, V95, P9484
[8]
Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination [J].
Guthrie, N ;
Gapor, A ;
Chambers, AF ;
Carroll, KK .
JOURNAL OF NUTRITION, 1997, 127 (03) :S544-S548
[9]
NK- and CD8+ T cell-mediated eradication of established tumors by peritumoral injection of CpG-containing oligodeoxynucleotides [J].
Kawarada, Y ;
Ganss, R ;
Garbi, N ;
Sacher, T ;
Arnold, B ;
Hämmerling, GJ .
JOURNAL OF IMMUNOLOGY, 2001, 167 (09) :5247-5253
[10]
Activation, differentiation, and migration of naive virus-specific CD8+ T cells during pulmonary influenza virus infection [J].
Lawrence, CW ;
Braciale, TJ .
JOURNAL OF IMMUNOLOGY, 2004, 173 (02) :1209-1218