{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:14:20Z","timestamp":1788545660175,"version":"build-2803163510"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"36","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104076"],"award-info":[{"award-number":["82104076"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473851"],"award-info":[{"award-number":["82473851"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China","award":["2022YFC3501905"],"award-info":[{"award-number":["2022YFC3501905"]}]},{"name":"National Key Research and Development Program of China","award":["2022YFC3501905"],"award-info":[{"award-number":["2022YFC3501905"]}]},{"name":"Technology Commission of Shanghai Municipal China","award":["22S21902400"],"award-info":[{"award-number":["22S21902400"]}]},{"name":"Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources","award":["2060302"],"award-info":[{"award-number":["2060302"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:p>\n                    The success of chimeric antigen receptor (CAR)-T cell therapy in hematologic malignancies has not been translated to solid tumors, primarily due to inadequate T cell infiltration and an immunosuppressive tumor microenvironment that drives T cell exhaustion. To address these challenges, we developed a tailored immunomodulatory drug-drug conjugate-based hydrogelator for the localized delivery of CAR-T cells targeting solid tumors. This hydrogel forms an in situ scaffold that serves as a sustained-release reservoir, enabling continuous co-delivery of CAR-T cells along with immunomodulatory agents\u2014NLG919 (an IDO-1 inhibitor) and\n                    <jats:sup>D<\/jats:sup>\n                    PPA-1 (a PD-L1 antagonistic peptide)\u2014to synergistically remodel the immunosuppressive tumor microenvironment and promote robust tumor recognition and elimination. Notably, this approach significantly enhances CAR-T cell infiltration and persistence, stimulates a potent endogenous tumor-specific immune response, while also establishing long-lasting immunological memory. In murine models of aggressive melanoma, metastatic breast cancer, and postoperative glioma, a single local administration of the hydrogel resulted in significant suppression of tumor growth, rechallenge, metastasis and recurrence. By integrating localized CAR-T cell delivery with in situ immune reprogramming, this system represents a versatile and clinically translatable platform that substantially improves the efficacy of CAR-T cell therapy against solid tumors.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee2120","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:58:46Z","timestamp":1788544726000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Supramolecular immunomodulatory hydrogelator potentiates CAR-T therapy with long-lasting endogenous immunity toward solid tumor eradication"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8682-2380","authenticated-orcid":true,"given":"Chenwei","family":"Jiang","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6341-1872","authenticated-orcid":true,"given":"Minglu","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingmei","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4737-0063","authenticated-orcid":true,"given":"Qi","family":"Shang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4286-0029","authenticated-orcid":true,"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"An","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4487-2791","authenticated-orcid":true,"given":"Junjie","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6108-2017","authenticated-orcid":true,"given":"Bing","family":"Feng","sequence":"additional","affiliation":[{"name":"Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0358-967X","authenticated-orcid":true,"given":"Feihu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103849"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-024-01216-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01207-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.03.019"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-02060-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39330-7"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12092567"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02079-8"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00832-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-02128-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010162"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-061119-015600"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1110-6"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40850-5"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.04.006"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwae075"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02875-1"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-025-00832-9"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0172-2"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-01002-x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa0984"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.017"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3226"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-021-01489-2"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4195"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47799-z"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c01748"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204621120"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz8985"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-020-0597-7"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202421703"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201506225"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00655-2"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01195-4"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-01100-5"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-024-01825-z"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn8264"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121872"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/2051-1426-2-21"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01245-x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00712-1"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114401"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.71"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202409796"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa4963"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2021.32"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401710"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.011"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12472"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54129-w"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg5841"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aee2120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:00:26Z","timestamp":1788544826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aee2120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":52,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2026,9,4]]}},"alternative-id":["10.1126\/sciadv.aee2120"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aee2120","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]},"assertion":[{"value":"2025-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaee2120"}}