biostudies-literatureFrancis DMAmerican Heart AssociationNIBIB NIH HHSSusan G. KomenU.S. Department of DefenseDepartment of Defense Peer Reviewed Cancer Research ProgramNCI NIH HHSNational Institutes of HealthNIH HHSNational Science Foundation121184https://www.ebi.ac.uk/biostudies/studies/S-EPMC8639654biostudies-literatureUnknown279Multiple small molecule immune modulators have been identified as synergistic with immune checkpoint blockade (ICB) in their effects on T lymphocytes, but are limited in their successful application to combination cancer immunotherapy due to their short in vivo retention and lack of affinity for T cells. We engineered an antibody-nanoparticle conjugate (ANC) platform consisting of 30 nm polymer nanoparticles that, due to their size and formulation, efficiently distribute after administration to lymph nodes, tissues highly enriched in lymphocytes that contribute to tumor control mediated by ICB. Displaying monoclonal antibodies against surface-expressed T cell markers, NP delivery in vivo to circulating and lymph node-resident lymphocytes was substantially enhanced, as was delivery of smallBiomaterialsDrug-eluting immune checkpoint blockade antibody-nanoparticle conjugate enhances locoregional and systemic combination cancer immunotherapy through T lymphocyte targeting.PMC8639654S10OD016264T32EB021962R01CA247484R01CA207619F31 CA150523R01 CA207619CA150523T32EB006343CCR15330478S10 OD016264T32 EB006343R01 CA247484T32 EB021962Sestito LFArcher PAManspeaker MPThomas SNSchudel AFrancis DMHeiler AJfalseDrug-eluting immune checkpoint blockade antibody-nanoparticle conjugate enhances locoregional and systemic combination cancer immunotherapy through T lymphocyte targeting.Multiple small molecule immune modulators have been identified as synergistic with immune checkpoint blockade (ICB) in their effects on T lymphocytes, but are limited in their successful application to combination cancer immunotherapy due to their short in vivo retention and lack of affinity for T cells. We engineered an antibody-nanoparticle conjugate (ANC) platform consisting of 30 nm polymer nanoparticles that, due to their size and formulation, efficiently distribute after administration to lymph nodes, tissues highly enriched in lymphocytes that contribute to tumor control mediated by ICB. Displaying monoclonal antibodies against surface-expressed T cell markers, NP delivery in vivo to circulating and lymph node-resident lymphocytes was substantially enhanced, as was delivery of small2021-01-01T00:00:00Z2021 Dec2026-05-05T03:14:53.214Z2025-04-05T10:17:02.577ZS-EPMC86396543467865010.1016/j.biomaterials.2021.121184