PDF(Pubmed)
Abstract：
In situ vaccination with immunostimulatory compounds is a demonstrated means to treat tumors preclinically. While these therapeutic effects have been attributed to the actions of T cells or innate immune activation, characterisation of the humoral immune response is seldom performed. This study aims to identify whether the injection of immunoadjuvants, Addavax (Adda) and cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG), intratumorally can influence the antibody response. Specifically, whether intratumoral injection of immunoadjuvants can alter the tumor-specific antibody target, titre and isotype. Following this, the study aimed to investigate whether serum obtained from in situ vaccinated mice could neutralise circulating tumor cells. Serum was obtained from mice bearing B16F10-OVA-Luc-GFP tumors treated with immunoadjuvants. Antibody targets\' titre and isotype were assessed by indirect ELISA. The ability of serum to neutralise circulating cancer cells was evaluated in a B16F10 pseudo-metastatic model. It was observed that tumor-bearing mice mount a specific anti-tumor antibody response. Antibody titre and target were unaffected by in situ vaccination with immunoadjuvants; however, a higher amount of IgG2c was produced in mice receiving Adda plus CpG. Serum from in situ vaccinated mice was unable to neutralise circulating B16F10 cells. Thus, this study has demonstrated that anti-tumor antibody isotype may be modified using in situ vaccination; however, this alone is not sufficient to neutralise circulating cancer cells.
摘要：
用免疫刺激化合物的原位疫苗接种是临床前治疗肿瘤的已证实的手段。虽然这些治疗效果归因于T细胞或先天免疫激活的作用，很少进行体液免疫应答的表征。本研究旨在确定是否注射免疫佐剂，Addavax（Adda）和胞嘧啶-硫代磷酸酯-鸟嘌呤寡核苷酸（CpG），瘤内可以影响抗体反应。具体来说,肿瘤内注射免疫佐剂是否可以改变肿瘤特异性抗体靶标，滴度和同种型。在此之后,该研究旨在研究从原位接种疫苗的小鼠获得的血清是否可以中和循环肿瘤细胞。从用免疫佐剂处理的携带B16F10-OVA-Luc-GFP肿瘤的小鼠获得血清。通过间接ELISA评估抗体靶标滴度和同种型。在B16F10假转移模型中评价血清中和循环癌细胞的能力。观察到荷瘤小鼠产生特异性抗肿瘤抗体应答。抗体滴度和靶标不受免疫佐剂原位接种的影响；然而，在接受Adda加CpG的小鼠中产生较高量的IgG2c。来自原位接种的小鼠的血清不能中和循环的B16F10细胞。因此，这项研究表明，抗肿瘤抗体同种型可以使用原位疫苗进行修饰；然而，这本身不足以中和循环癌细胞。
