Tumor cell lysate-loaded immunostimulatory spherical nucleic acids as therapeutics for triple-negative breast cancer

Proceedings of the National Academy of Sciences of the United States of America
Cassandra E CallmannChad Mirkin

Abstract

Highly heterogenous cancers, such as triple-negative breast cancer (TNBC), remain challenging immunotherapeutic targets. Herein, we describe the synthesis and evaluation of immunotherapeutic liposomal spherical nucleic acids (SNAs) for TNBC therapy. The SNAs comprise immunostimulatory oligonucleotides (CpG-1826) as adjuvants and encapsulate lysates derived from TNBC cell lines as antigens. The resulting nanostructures (Lys-SNAs) enhance the codelivery of adjuvant and antigen to immune cells when compared to simple mixtures of lysates with linear oligonucleotides both in vitro and in vivo, and reduce tumor growth relative to simple mixtures of lysate and CpG-1826 (Lys-Mix) in both Py230 and Py8119 orthotopic syngeneic mouse models of TNBC. Furthermore, oxidizing TNBC cells prior to lysis and incorporation into SNAs (OxLys-SNAs) significantly increases the activation of dendritic cells relative to their nonoxidized counterparts. When administered peritumorally in vivo in the EMT6 mouse mammary carcinoma model, OxLys-SNAs significantly increase the population of cytotoxic CD8+ T cells and simultaneously decrease the population of myeloid derived suppressor cells (MDSCs) within the tumor microenvironment, when compared with Lys-SNA...Continue Reading

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Citations

Jan 22, 2021·Advanced Healthcare Materials·Arezoo EsrafiliAbhinav P Acharya
Nov 6, 2020·Pharmaceuticals·Thomas R Holmes, Amy S Paller
Nov 21, 2020·Drug Discovery Today·Bo ChenGang Guo
Jun 4, 2021·ACS Central Science·Cassandra E CallmannChad A Mirkin
Sep 2, 2021·Bioactive Materials·Lei WuJun Yue
Sep 22, 2021·ACS Applied Materials & Interfaces·Wuliang ZhangChad A Mirkin
Sep 4, 2021·Angewandte Chemie·Junlin SunXiaoqing Liu

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