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However, the optimal dose and order of administration of different agents remain elusive. To address this dilemma, multiple agents are often grafted together to construct \u201call\u2010in\u2010one\u201d totipotent drugs, but this usually comes at the cost of a lack of synergy between the agents. Herein, by comprehensively analyzing the conserved sites of the immune checkpoint and TME drug targets, peptide secondary structures, assembly properties, and other physicochemical properties, a high\u2010content peptide library is designed. By using the \u201c3D\u2010molecular\u2010evolution\u201d screening strategy, an efficient and totipotent \u201call\u2010in\u2010one\u201d peptide (TAP) is obtained, which possesses the abilities of self\u2010assembling, blocking the PD\u20101\/PD\u2010L1\u00a0axis, inhibiting Rbm38\u2010eIF4E complex formation, and activating p53. It is shown that in mice treated with TAP, with either subcutaneous tumors or patient\u2010derived xenografts, PD\u2010L1\u00a0is blocked, with increased activation of both T and NK cells whilst reversing the immunosuppressive TME. Moreover, TAP can mitigate tumor activity and suppress tumor growth, showing superior therapeutic effect over antibody\u2010based drugs.<\/jats:p>","DOI":"10.1002\/adma.202207330","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T07:19:32Z","timestamp":1666163972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["A Totipotent \u201cAll\u2010In\u2010One\u201d Peptide Sequentially Blocks Immune Checkpoint and Reverses the Immunosuppressive Tumor Microenvironment"],"prefix":"10.1002","volume":"35","author":[{"given":"Limin","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering Ministry of Industry and Information Technology Key Laboratory of Cluster Science of Ministry of Education Beijing Key Laboratory of Photoelectronic\/Electro\u2010photonic Conversion Materials School of Chemistry and Chemical Engineering Beijing Institute of Technology  Beijing 100081 P. 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