Impact of ligand size and conjugation chemistry on the performance of universal chimeric antigen receptor T-cells for tumor killing

Pellegrino, Christian; Favalli, Nicholas; Sandholzer, Michael; Volta, Laura; Bassi, Gabriele; Millul, Jacopo; Cazzamalli, Samuele; Matasci, Mattia; Villa, Alessandra; Myburgh, Renier; Manz, Markus G; Neri, Dario

doi:10.1021/acs.bioconjchem.0c00258

Citations

Citation copied

Pellegrino, C., Favalli, N., Sandholzer, M., Volta, L., Bassi, G., Millul, J., Cazzamalli, S., Matasci, M., Villa, A., Myburgh, R., Manz, M. G., & Neri, D. (2020). Impact of ligand size and conjugation chemistry on the performance of universal chimeric antigen receptor T-cells for tumor killing. Bioconjugate Chemistry, 31(7), 1775–1783. https://doi.org/10.1021/acs.bioconjchem.0c00258

Abstract

All Universal Chimeric Antigen Receptor T-cells (UniCAR T-cells) are T-cells which have been engineered to recognize a haptenated ligand. Due to this feature, UniCAR T-cells have the potential to mediate a potent and selective tumor killing only in the presence of a haptenated tumor ligand, thus avoiding the long-lasting biocidal effects of conventional CAR T-cells. We have used fluorescein-labeled versions of small organic ligands and different antibody formats specific to carbonic anhydrase IX (a tumor-associated antigen) in order t