Shin Jung Min, Song Seok Ho, Vijayakameswara Rao N, Lee Eun Sook, Ko Hyewon, Park Jae Hyung
1School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419 Republic of Korea.
2Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Suwon, 16419 Republic of Korea.
Biomater Res. 2018 Aug 14;22:21. doi: 10.1186/s40824-018-0131-0. eCollection 2018.
Antigen-specific cytotoxic T lymphocytes (CTLs), which eliminate target cells bearing antigenic peptides presented by surface major histocompatibility complex (MHC) class I molecules, play a key role in cancer immunotherapy. However, the majority of tumors are not immunologically rejected since they express self-antigens which are not recognized by CTLs as foreign. To foreignize these tumors for CTL-mediated immunological rejection, it is essential to develop carriers that can effectively deliver foreign antigens to cancer cells.
A polymeric conjugate, composed of a carboxymethyl dextran (CMD) as the backbone and ovalbumin (OVA) as a model foreign antigen, was prepared to investigate its potential as the antigen carrier for cancer immunotherapy.
An in vitro cellular uptake study showed that the conjugate was successfully taken up by TC-1 cervical cancer cells. When CMD-OVA was systemically administered to tumor-bearing mice, the strong fluorescence signal was observed at the tumor site over the whole period of time period, suggesting high tumor targetability of the conjugate. Compared to free OVA, CMD-OVA induced significantly higher antigen presentation at the tumor site.
The CMD-OVA conjugate can effectively deliver the antigen to the tumor site, implying its high potential as the antigen carrier for cancer immunotherapy.
抗原特异性细胞毒性T淋巴细胞（CTLs）可清除携带由表面主要组织相容性复合体（MHC）I类分子呈递的抗原肽的靶细胞，在癌症免疫治疗中起关键作用。然而，大多数肿瘤不会被免疫排斥，因为它们表达的自身抗原不被CTLs识别为外来抗原。为了使这些肿瘤能够被CTL介导的免疫排斥，开发能够有效地将外来抗原递送至癌细胞的载体至关重要。
制备了一种以羧甲基葡聚糖（CMD）为骨架、卵清蛋白（OVA）为模型外来抗原的聚合物偶联物，以研究其作为癌症免疫治疗抗原载体的潜力。
体外细胞摄取研究表明，该偶联物成功被TC-1宫颈癌细胞摄取。当将CMD-OVA全身给药于荷瘤小鼠时，在整个时间段内肿瘤部位均观察到强烈的荧光信号，表明该偶联物具有高肿瘤靶向性。与游离OVA相比，CMD-OVA在肿瘤部位诱导的抗原呈递显著更高。
CMD-OVA偶联物能够有效地将抗原递送至肿瘤部位，这意味着它作为癌症免疫治疗抗原载体具有很高的潜力。
