ArticleAntibody therapeutics2026
DOTAM-TCB: Universal Small Molecule-guided Hapten- and T Cell-bispecific Antibodies for Cancer Immunotherapy.
Article in Antibody therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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18 authors.
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Abstract
Background: 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. Methods: 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 Ca Results: Conclusions: 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.
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