{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:58:28Z","timestamp":1790848708491,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019209","name":"Roche Glycart AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor heterogeneity has been identified as a major roadblock for cancer immunotherapy. To overcome this, universal effector cell engagers with interchangeable tumor-targeting adaptors have been developed. Current concepts in this field consist of antibody-based adaptors. Small-molecule (SM) ligands, on the other hand, infiltrate tissues rapidly, have short half-lives, and are potentially orally available. Therefore, we hypothesized that utilizing SM adaptors, combined with effector antibodies, could represent an attractive off-the-shelf therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we introduce the development of target-agnostic, small-molecule-guided hapten- and T cell-bispecific (TCB) antibodies with high affinity between the adaptor-effector pair. Specifically, we designed SM adaptors based on known tumor-targeting ligands with specificity to the antigens folate receptor 1 (FOLR1), prostate-specific membrane antigen (PSMA) and carbonic anhydrase IX (CAIX), and conjugated them to Ca2+-loaded 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (DOTAM) as a hapten. As an effector antibody, we designed DOTAM-specific T cell bispecific antibodies (DOTAM-TCB) with femtomolar (fM) affinity for the hapten.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro experiments showed in-solution assembly of stable adaptor-effector complexes. Additionally, T cell-mediated tumor killing was initiated by the universal DOTAM-TCB when combined with adaptors across various tumor cells. Ex vivo study of CAIX-directed Ca-DOTAM-acetazolamide (Ca-DOTAM-AAZ) with DOTAM-TCB showed potent activation of T cells against murine-engrafted human HT-29 tumor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The studies described here demonstrate proof-of-concept for using hapten-containing small molecules as adaptors for effective universal T cell engager-based cancer immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/abt\/tbag038","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:41:43Z","timestamp":1785498103000},"page":"535-549","source":"Crossref","is-referenced-by-count":0,"title":["DOTAM-TCB: Universal Small Molecule-guided Hapten- and T Cell-bispecific Antibodies for Cancer 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