Abstract
Dendritic cell (DC) vaccines are a newly emerging immunotherapeutic approach for the treatment and prevention of cancer, but major challenges still remain particularly with respect to clinical efficacy. Engineering and optimization of adjuvant formulations for DC-based vaccines is one strategy through which more efficacious treatments may be obtained. In this study, we developed a new ex vivo approach for DC vaccine preparation. We evaluated two highly purified mixed polysaccharide fractions from the root of Astragalus membranaceus and Codonopsis pilosulae, named Am and Cp, for their use in enhancing the efficiency of a DC-based cancer vaccine against metastasis of 4T1 mammary carcinoma in mice. Mixed lymphocyte reaction showed all Am-, Cp- and [Am+Cp]-treated DCs enhanced mouse CD4+ and CD8+ T-cell proliferation. [Am+Cp]-treated DCs exhibited the strongest anti-4T1 metastasis activity in test mice. Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs. Bioinformatics analysis of the cytokine array data from treated DCs identified that [Am+Cp] is efficacious in activation of specific immune functions via mediating the expression of cytokines/chemokines involved in the recruitment and differentiation of defined immune cells. Biochemical analysis revealed that Am and Cp are composed mainly of polysaccharides containing a high level (70–95%) glucose residues, but few or no (< 1%) mannose residues. In summary, our findings suggest that the specific plant polysaccharides Am and Cp extracted from traditional Chinese medicines can be effectively used instead of bacterial LPS as a potent adjuvant in the formulation of a DC-based vaccine for cancer immunotherapies.
Highlights
Breast cancer is one of the most common cancers in women worldwide, and 5% to 10% of breast cancer patients are diagnosed as metastatic [1]
In order to characterize the applicability, and biosafety of the candidate adjuvants for a DCbased cancer vaccine, the cytotoxicity of Cp, Am and [Am+Cp] and 4T1 tumor cell lysate on test Dendritic cell (DC) was determined by MTT assay
We previously showed that the anti-melanoma efficiency of a DC-based cancer vaccine is mainly by activation of T-cell expansion and activation [16]
Summary
Breast cancer is one of the most common cancers in women worldwide, and 5% to 10% of breast cancer patients are diagnosed as metastatic [1]. Our recent study showed that the cell lysate derived from shikonin-treated tumor cells and LPS in combination resulted in specific DC activation, and the DC-based vaccine effectively enhanced the priming of Th1/Th17 effector cells for induction of a potent anti-tumor effect [9]. Another important issue for optimization of anti-tumor response for successful therapeutic vaccination is the active state of DCs to be delivered as cellbased vaccines [6,10]. Following the recent FDA approvals of these pioneering cell-based vaccines and cancer vaccine adjuvants, there is a need to better understand the science behind the use of TLR agonists (including specific polysaccharides) as adjuvants to aid the development of further therapeutic TCL-loaded DC-based cancer vaccines
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