Targeting Adaptive and Innate Immune Responses with Covalent Aptamers.

Authors

Savannah Albright, Avani Parikh, Mary Cacace, Carolyn Rosenblum, Michael Dorogan, Jason Lohmueller, Alexander Deiters

Published in

Journal of the American Chemical Society. Volume 148. Issue 32. Pages 34928-34937. Aug 19, 2026.

Abstract

Covalent aptamers have recently found initial success as tools for fast and selective transfer of labels to target proteins. 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.

PMID:
42619145
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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