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Here, aptamers targeting protein tyrosine kinase 7 (PTK7) and the mesenchymal-epithelial transition factor (cMet) were functionalized with electrophiles capable of covalently transferring small-molecule immune recruiters. Capitalizing on biotin transfer, aptamers were utilized to trigger activation of universal anti-biotin chimeric antigen receptor (CAR) T cells resulting in selective lysis of PTK7- and cMet-positive cells. Additionally, a cleavable electrophile of 2,4-dinitrophenyl (DNP) hapten transfer was synthesized and utilized for the selective modification of cell surface PTK7 and cMet. The DNP modification elicited the selective activation of complement-dependent cytotoxicity (CDC). These results demonstrate the potential of covalent aptamers as immune-activating and cancer-cell-killing agents.<\/jats:p>","DOI":"10.1021\/jacs.6c10475","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:02:07Z","timestamp":1786363327000},"page":"34928-34937","source":"Crossref","is-referenced-by-count":0,"title":["Targeting\nAdaptive and Innate Immune Responses with\nCovalent Aptamers"],"prefix":"10.1021","volume":"148","author":[{"given":"Savannah","family":"Albright","sequence":"first","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4083-0987","authenticated-orcid":true,"given":"Avani","family":"Parikh","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15213"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Cacace","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Rosenblum","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-2539","authenticated-orcid":true,"given":"Michael","family":"Dorogan","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Lohmueller","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15213"]},{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0234-9209","authenticated-orcid":true,"given":"Alexander","family":"Deiters","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]},{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"1","key":"2026081910214729100_cit1","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/s12943-025-02305-x","article-title":"Advances in\ncancer immunotherapy: historical perspectives, current developments,\nand future directions","volume":"24","author":"Zhang","year":"2025","journal-title":"Mol. 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