Targeting of antigens to B lymphocytes via CD19 as a means for tumor vaccine development.
Targeting of antigens to B lymphocytes via CD19 as a means for tumor vaccine development.
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DOI：
10.4049/jimmunol.1203216
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发表时间：
2013-06-01
期刊：
影响因子：
--
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Ma Y;Xiang D;Sun J;Ding C;Liu M;Hu X;Li G;Kloecker G;Zhang HG;Yan J
针对肿瘤细胞表面Ags的抗体治疗已证明对某些癌症有显著疗效。然而，它是昂贵的，并且随着时间的推移，患者经常产生获得性耐药性。在抗体治疗耐药的情况下，T细胞反应已被证明在控制疾病进展中是必不可少的。因此，产生持续的Ab反应和T细胞反应的疫苗接种可能更有效和经济。在这里，我们开发了一种疫苗接种策略，通过CD19单链可变片段miniAb将蛋白Ags靶向到B细胞。通过使用肿瘤相关Ag (TAA) her-2/新细胞外结构域（ECD），我们发现CD19和BCR的共同作用诱导了B细胞的完全激活，产生高滴度的抗体，增强了CD4 Th2应答和CD8 T细胞的激活和分化。这些抗体竞争性地抑制人源化her-2/ new Ab结合，能够激活补体并抑制人乳腺癌体外生长。用小鼠乳腺癌模型在体内证明了治疗效果。此外，her-2/neu的四种不同ECDs可以靶向B细胞产生针对具有不同抗肿瘤特性的特定结构域的抗体。这种方法可能为疫苗开发提供一条成本显著降低的新途径，不仅可用于癌症治疗，也可用于感染性病原体。
Ab therapy against surface Ags on tumor cells has demonstrated significant efficacy for some cancers. However, it is costly and patients frequently develop acquired resistance over time. In cases of Ab therapy resistance, T cell responses have been shown to be essential in controlling disease progression. Thus, vaccination that generates a sustained Ab response as well as a T cell response may be more effective and economical. Here, we have developed a vaccination strategy by targeting protein Ags to B cells via a CD19 single chain variable fragment miniAb. By using the tumor-associated Ag (TAA) her-2/neu extracellular domain (ECD), we showed that the co-engagement of CD19 and BCR induced full B cell activation to produce a high titer of Abs and enhanced CD4 Th2 response and CD8 T cell activation and differentiation. These Abs competitively inhibited humanized her-2/neu Ab binding and were capable of activating the complement and inhibiting human breast cancer growth in vitro. Therapeutic efficacy was demonstrated in vivo using murine mammary carcinomas models. Furthermore, four different ECDs of her-2/neu could be targeted to B cells to generate Abs against particular domains with different anti-tumor properties. This approach may offer a new avenue for vaccine development with significantly lower cost which may be usable not only for cancer therapy but also for infectious agents.
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影响因子：
2.2
作者：
Benedict, CA;MacKrell, AJ;Anderson, WF
通讯作者：
Anderson, WF
DOI：
10.4049/jimmunol.0903009
发表时间：
2010-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
DiLillo DJ;Yanaba K;Tedder TF
通讯作者：
Tedder TF
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
64.8
作者：
Cho, HS;Mason, K;Leahy, DJ
通讯作者：
Leahy, DJ
影响因子：
3.3
作者：
Fleck, Leonard M.
通讯作者：
Fleck, Leonard M.