我们在这里提出了一种新的方法，通过整合抗体介导的免疫治疗和光动力疗法（PDT）来提高抗体药物偶联物（ADC）的疗效，利用基于聚氧化丙烯酸酯聚合物连接剂的抗体-光敏剂偶联物（APC）平台进行联合治疗系统。为了特异性地靶向KRAS突变癌细胞，我们通过点击化学（CMPXC）合成了一个抗表皮生长因子受体（EGFR）的抗体丙种类单抗（cetuximab）与聚氧化丙烯酸酯聚合物连接剂偶联，以及光敏剂叶绿素e6（MPXC）。CMPXC在激光治疗下具有细胞毒性，通过抑制与ERK和AKT蛋白相关的KRAS下游信号通路，通过RNA测序分析得到的结果证实，这导致90%的细胞死亡。在KRAS突变结直肠癌（CRC）小鼠模型中，CMPXC与单独应用cetuximab相比，显著增强了抗肿瘤疗效，使肿瘤生长减少了86%。此外，CMPXC治疗导致树突状细胞和引发细胞毒性T细胞分别增加了2.24倍和1.75倍，突显了该方法的免疫激活潜力。我们的研究结果表明，APC平台解决了ADC开发和EGFR靶向治疗所面临的挑战，包括抗体介导免疫治疗和PDT的协同优势。本文受版权保护。保留所有权利。

Here, we present a novel approach to improve the efficacy of antibody-drug conjugates (ADC) by integrating antibody-mediated immunotherapy and photodynamic therapy (PDT) in a combination therapy system utilizing an antibody-photosensitizer conjugate (APC) platform based on a poloxamer polymer linker. To specifically target KRAS-mutated cancer cells, we synthesized an antibody anti-epidermal growth factor receptor (EGFR), cetuximab, with a poloxamer linker coupled with the photosensitizer chlorin e6 (MPXC) through click chemistry (CMPXC). CMPXC was cytotoxic upon laser treatment, achieving a 90% cell death by suppressing KRAS downstream signaling pathways associated with ERK and AKT proteins, confirmed using RNA sequencing analysis. In KRAS-mutated colorectal cancer (CRC) mouse models, CMPXC significantly enhanced antitumor efficacy compared with cetuximab treatment alone, resulting in an 86% reduction in tumor growth. Furthermore, CMPXC treatment led to a 2.24- and 1.75-fold increase in dendritic and priming cytotoxic T cells, respectively, highlighting the immune-activating potential of this approach. Our findings suggest that the APC platform addresses the challenges associated with ADC development and EGFR-targeted therapy, including the synergistic advantages of antibody-mediated immunotherapy and PDT. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.