Therapeutic antitumor efficacy of B cells loaded with tumor-derived autophagasomes vaccine (DRibbles)

装载肿瘤衍生自噬体疫苗的B细胞的抗肿瘤治疗功效(DRibbles)

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作者:Hongyan Ren, Simin Zhao, Weixia Li, Huixia Dong, Meng Zhou, Meng Cao, Hong-Ming Hu, Li-xin Wang

Abstract

Tumor-derived autophagosomes (DRibble) selectively capture tumor-specific antigens and induce a dramatic T-cell activation and expansion when injected into lymph nodes of naive mice. Both dendritic and B cells can efficiently cross-prime antigen-specific T cells. In this report, we demonstrated that a booster vaccination with naive B cells loaded with DRibbles eradicated E.G7-OVA tumors in mice that were previously treated with adoptive transfer naive OT-I T cells and intranodal immunization with DRibbles derived from E.G7 tumors. The antitumor efficacy was accompanied by a heighten number of tumor-specific interferon-γ-producing T cells and antibodies. However, the same treatment in the absence of adoptive T-cell transfer exhibited a limited efficacy. In contrast, when DRibble-loaded B cells were activated with CpG and anti-CD40 antibody before use as booster vaccines, established E.G7 tumors were completely eradicated in the absence of T-cell transfer. Therefore, our results document that B cells could efficiently cross-present tumor-specific antigens captured by DRibbles and suggest that naive B cells can be deployed as an effective and readily accessible source of antigen-presenting cells for cancer immunotherapy clinical trials.

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