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However, it is challenging to accurately study the efficacy of immunotherapy based on human\u2010derived cells through animal experiments due to xenogeneic immune rejection. Herein, a personalized and precise strategy to evaluate the effectiveness of immunotherapy using the blood samples of cancer patients is presented. Through the utilization of multiple cancer\u2010targeting delivery system decorated with the epidermal growth factor receptor (EGFR)\u2010specific aptamer CL4 and the AXL\u2010specific aptamer GL21.T to achieve superior efficiency in delivering the genome editing plasmid for MUC1 knockout, effective modulation on the behavior of circulating malignant cells (CMCs) is realized. After genome editing, both mucin 1 (MUC1) and programmed death\u2010ligand 1 (PD\u2010L1) are significantly downregulated in CMCs. The elimination of immunosuppression results in markedly enhanced secretion of pro\u2010inflammatory anticancer cytokines encompassing interleukins 2, 12, and 15 and interferon\u2010\u03b3 by immune cells. The study not only provides a strategy to overcome immunosuppression but also yields critical insights for personalized immunotherapy approaches.<\/jats:p>","DOI":"10.1002\/adhm.202401223","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T05:58:06Z","timestamp":1729663086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Multiple Targeting Genome Editing System for Remodulation of Circulating Malignant Cells to Eliminate Cancer Immunosuppression and Restore Immune Responses"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiao\u2010He","family":"Ren","sequence":"first","affiliation":[{"name":"School of Life Sciences Anhui Medical University  Hefei Anhui 230011 China"},{"name":"College of Chemistry and Molecular Sciences Wuhan University  Wuhan Hubei 430072 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