Therapeutic antitumor efficacy of B cells loaded with tumor-derived autophagasomes vaccine (DRibbles).
Therapeutic antitumor efficacy of B cells loaded with tumor-derived autophagasomes vaccine (DRibbles).
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负载肿瘤源性自噬体疫苗 (DRibbles) 的 B 细胞的治疗抗肿瘤功效
DOI：
10.1097/cji.0000000000000051
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Wang LX
中科院分区：
文献类型：
--
作者：
Ren H;Zhao S;Li W;Dong H;Zhou M;Cao M;Hu HM;Wang LX
补充数字内容可在文本中找到。肿瘤来源的自噬体（DRibble）选择性地捕获肿瘤特异性抗原，并在注射到幼稚小鼠的淋巴结中时诱导显著的T细胞活化和扩增。树突状细胞和B细胞都可以有效地交叉致敏抗原特异性T细胞。在本报告中，我们证明了用装载有DRibbles的幼稚B细胞的加强疫苗接种根除了先前用过继转移幼稚OT-I T细胞和用源自E.G7肿瘤的DRibbles的结内免疫处理的小鼠中的E.G7-OVA肿瘤。抗肿瘤疗效伴随着肿瘤特异性产生干扰素-γ的T细胞和抗体数量的增加。然而，在不存在过继性T细胞转移的情况下，相同的治疗表现出有限的功效。相反，当在用作加强疫苗之前用CpG和抗-CD 40抗体活化DRibble负载的B细胞时，在不存在T细胞转移的情况下，建立的E. G7肿瘤被完全根除。因此，我们的结果证明B细胞可以有效地交叉呈递被DRibbles捕获的肿瘤特异性抗原，并表明幼稚B细胞可以被部署为用于癌症免疫治疗临床试验的有效且容易获得的抗原呈递细胞来源。
Supplemental Digital Content is available in the text. 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.