肿瘤特异性突变会产生对癌症独特的新抗原，可以被免疫系统识别，成为治疗性癌症疫苗吸引人的靶点。由于绝大多数肿瘤突变都是患者特异性的，因此癌症疫苗的设计与个体化治疗策略兼容是至关重要的。质粒DNA疫苗在临床前模型中证明了癌症新抗原的免疫原性和抗肿瘤能力。此外，早期临床试验评估个性化新抗原疫苗显示了良好的安全性，并证明其能够引发特异性免疫反应对疫苗新抗原。通过将体内预测的新抗原与与抗原呈递细胞（APCs）表面受体具有亲和力的分子（例如趋化因子（C-C基序）配体19（CCL19））融合，我们设计了一种以APCs为靶向的癌症疫苗，并评估了它们在BALB/c同基因临床前肿瘤模型中诱导T细胞反应和抗肿瘤效力的能力。在本研究中，我们证明了将抗原呈递细胞（APC）结合分子加入DNA编码的癌症新抗原中，可以改善新抗原特异性T细胞反应和质粒DNA疫苗的抗肿瘤效力。量效相关评估和新抗原特异性T细胞反应的纵向分析表明，将APC结合分子与个体化肿瘤抗原的传递相结合，有潜力改善治疗性DNA癌症疫苗的临床有效性。我们的发现表明了APC靶向策略提升个性化DNA癌症疫苗的潜力，同时也承认有进一步研究来探究其作用的分子机制，并将临床前结果转化为有效的癌症治疗手段的需求。版权所有© 2023 Barrio-Calvo、Kofoed、Holste、Sørensen、Viborg、Kringelum、Kleine-Kohlbrecher、Steenmans、Thygesen、Rønø和Friis.

Tumor-specific mutations generate neoepitopes unique to the cancer that can be recognized by the immune system, making them appealing targets for therapeutic cancer vaccines. Since the vast majority of tumor mutations are patient-specific, it is crucial for cancer vaccine designs to be compatible with individualized treatment strategies. Plasmid DNA vaccines have substantiated the immunogenicity and tumor eradication capacity of cancer neoepitopes in preclinical models. Moreover, early clinical trials evaluating personalized neoepitope vaccines have indicated favorable safety profiles and demonstrated their ability to elicit specific immune responses toward the vaccine neoepitopes.By fusing in silico predicted neoepitopes to molecules with affinity for receptors on the surface of APCs, such as chemokine (C-C motif) ligand 19 (CCL19), we designed an APC-targeting cancer vaccine and evaluated their ability to induce T-cell responses and anti-tumor efficacy in the BALB/c syngeneic preclinical tumor model.In this study, we demonstrate how the addition of an antigen-presenting cell (APC) binding molecule to DNA-encoded cancer neoepitopes improves neoepitope-specific T-cell responses and the anti-tumor efficacy of plasmid DNA vaccines. Dose-response evaluation and longitudinal analysis of neoepitope-specific T-cell responses indicate that combining APC-binding molecules with the delivery of personalized tumor antigens holds the potential to improve the clinical efficacy of therapeutic DNA cancer vaccines.Our findings indicate the potential of the APC-targeting strategy to enhance personalized DNA cancer vaccines while acknowledging the need for further research to investigate its molecular mechanism of action and to translate the preclinical results into effective treatments for cancer patients.Copyright © 2023 Barrio-Calvo, Kofoed, Holste, Sørensen, Viborg, Kringelum, Kleine-Kohlbrecher, Steenmans, Thygesen, Rønø and Friis.