Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 43000 Selangor, Malaysia.
BMC Cancer. 2010 Jan 6;10:5. doi: 10.1186/1471-2407-10-5.
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.
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.
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.
Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.
树突状细胞（DCs）具有处理和向 T 细胞呈递抗原以及刺激免疫反应的能力，因此具有用于癌症免疫治疗的潜力。然而，基于树突状细胞的疫苗在小鼠和人类中仅对已建立的肿瘤表现出最小的有效性。适当的佐剂的使用增强了基于树突状细胞的癌症疫苗治疗肿瘤的功效。
在这项研究中，我们使用富含生育三烯酚的馏分（TRF），一种无毒的天然化合物，作为佐剂来增强 DC 疫苗治疗小鼠乳腺肿瘤的效力。在小鼠模型中，将 6 周龄雌性 BALB/c 小鼠皮下注射 DC，并每天口服补充 TRF（DC+TRF）和用肿瘤裂解物脉冲的 DC（DC+TL）。实验小鼠还接受了用肿瘤裂解物脉冲并每天口服补充 TRF 的 DC 注射（DC+TL+TRF），而两组动物则每天补充载体油（对照）和 TRF（TRF）。三次接种后，将小鼠在乳腺垫中接种 4T1 细胞以诱导肿瘤。
我们的研究表明，与对照组相比，TRF 与用肿瘤裂解物脉冲的 DC（DC+TL+TRF）联合皮下注射可显著抑制 4T1 乳腺肿瘤细胞的生长。从鼠脾细胞中分析细胞因子的产生显示，与对照组、未用 TRF 注射的 DC 组、用肿瘤裂解物脉冲的 DC 组和单独用 TRF 补充的小鼠相比，实验小鼠（DC+TL+TRF）中 IFN-γ和 IL-12 的产生显著增加。在外周血中观察到更多的细胞毒性 T 细胞（CD8）和自然杀伤细胞（NK）。
我们的研究表明，TRF 有可能成为增强基于树突状细胞的免疫疗法的佐剂。
