The cell-free approach to foreignizing tumor cells with non-self antigens has received increasing attention as a method to induce cytotoxic T lymphocyte (CTL)-mediated immunological rejection of tumors, because the clinical translation of the conventional CTL-based cancer immunotherapies has been limited by a complicated manufacturing process and autotransplantation. In this study, we prepared matrix metalloproteinase 9 (MMP9)-responsive polymeric conjugates consisting of PEGylated hyaluronic acid (HA) as the targeting moiety and ovalbumin (OVA) as the model foreign antigen. The MMP9-cleavable linker was introduced between PEG and the HA backbone to facilitate the detachment of the PEG corona from the conjugate at the tumor site. From the in vitro cellular uptake study, it was revealed that the conjugate was effectively taken up by the CD44-expressing TC-1 cancer cells in the presence of MMP9 via receptor-mediated endocytosis. When the conjugate was systemically administered into the tumor-bearing mice with endogenous OVA-specific CTLs, the tumor growth was markedly inhibited, which was attributed to the significant antigen presentation on the tumor cells. Overall, the MMP9-responsive conjugates bearing foreign antigens might have the potential as an alternative to CTL-based cancer immunotherapeutics.

作为诱导细胞毒性T淋巴细胞（CTL）介导的肿瘤免疫排斥的一种方法，采用非自身抗原异化肿瘤细胞的无细胞方法已受到越来越多的关注，因为常规基于CTL的癌症免疫疗法的临床翻译已被广泛采用。受制于复杂的制造过程和自动移植。在这项研究中，我们制备了基质金属蛋白酶9（MMP9）响应聚合物共轭物，由聚乙二醇化透明质酸（HA）作为靶向部分和卵清蛋白（OVA）作为模型外来抗原。将MMP9可裂解的接头引入PEG和HA骨架之间，以促进PEG电晕从结合物在肿瘤位点上脱离。从体外细胞摄取研究表明，在MMP9存在下，CD44表达的TC-1癌细胞通过受体介导的内吞作用有效地吸收了结合物。当将结合物与内源性OVA特异性CTL全身给药于荷瘤小鼠时，肿瘤的生长受到明显抑制，这归因于肿瘤细胞上显着的抗原呈递。总体而言，带有外源抗原的MMP9反应性偶联物可能具有替代基于CTL的癌症免疫疗法的潜力。