A Dual Immunotherapy Nanoparticle Improves T‐Cell Activation and Cancer Immunotherapy |
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Authors: | Yu Mi Christof C Smith Feifei Yang Yanfei Qi Kyle C Roche Jonathan S Serody Benjamin G Vincent Andrew Z Wang |
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Affiliation: | 1. Laboratory of Nano‐ and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, Lineberger Comprehensive Cancer Center, Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;2. Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;3. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Haidian District, Beijing, P. R. China;4. School of Public Health, Jilin University, Changchun, Jilin, P. R. China |
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Abstract: | Combination immunotherapy has recently emerged as a powerful cancer treatment strategy. A promising treatment approach utilizes coadministration of antagonistic antibodies to block checkpoint inhibitor receptors, such as antiprogrammed cell death‐1 (aPD1), alongside agonistic antibodies to activate costimulatory receptors, such as antitumor necrosis factor receptor superfamily member 4 (aOX40). Optimal T‐cell activation is achieved when both immunomodulatory agents simultaneously engage T‐cells and promote synergistic proactivation signaling. However, standard administration of these therapeutics as free antibodies results in suboptimal T‐cell binding events, with only a subset of the T‐cells binding to both aPD1 and aOX40. Here, it is shown that precise spatiotemporal codelivery of aPD1 and aOX40 using nanoparticles (NP) (dual immunotherapy nanoparticles, DINP) results in improved T‐cell activation, enhanced therapeutic efficacy, and increased immunological memory. It is demonstrated that DINP elicits higher rates of T‐cell activation in vitro than free antibodies. Importantly, it is demonstrated in two tumor models that combination immunotherapy administered in the form of DINP is more effective than the same regimen administered as free antibodies. This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology. |
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Keywords: | cancer immunotherapy checkpoint inhibitor combination therapy polymeric nanoparticle T‐cell agonist |
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