Approximately 15–40% of all cancers develop metastases in the central nervous system (CNS), yet few therapeutic options exist to treat them. Cancer therapies based on monoclonal antibodies are widely successful, yet have limited efficacy against CNS metastases, owing to the low levels of the drug reaching the tumour site. Here, we show that the encapsulation of rituximab within a crosslinked zwitterionic polymer layer leads to the sustained release of rituximab as the crosslinkers are gradually hydrolysed, enhancing the CNS levels of the antibody by approximately tenfold with respect to the administration of naked rituximab. When the nanocapsules were functionalized with CXCL13—the ligand for the chemokine receptor CXCR5, which is frequently found on B-cell lymphoma—a single dose led to improved control of CXCR5-expressing metastases in a murine xenograft model of non-Hodgkin lymphoma, and eliminated lymphoma in a xenografted humanized bone marrow–liver–thymus mouse model. Encapsulation and molecular targeting of therapeutic antibodies could become an option for the treatment of cancers with CNS metastases.
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The authors declare that all data supporting the results of this study are available within the paper and its Supplementary Information files. Source data collected in this study are available from the corresponding author upon request.
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This work was supported by the UCLA AIDS Institute HIV Extinction Project funded by the McCarthy Family Foundation (to M.K.), NIH grants RO1 CA232015 and RO1 AI110200 (to M.K.), U19AI117941 (to I.S.Y.C.) and R21 AI114433 (to I.S.Y.C.), and the California HIV/AIDS Research Grants Program (ID15-LA-050 to D.Widney). Equipment located at the UCLA AIDS Institute is supported by the James B. Pendleton Charitable Trust. Cell sorting was performed in the CFAR Flow Cytometry Core Facility supported by NIH grants P30 CA016042 and 5P30 AI028697.
I.S.Y.C. has a financial interest in CSL Behring. The remaining authors declare no competing interests.
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Wen, J., Wu, D., Qin, M. et al. Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice. Nat Biomed Eng 3, 706–716 (2019). https://doi.org/10.1038/s41551-019-0434-z
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