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Abstract Skeletal metastasis is common in patients with advanced breast cancer and often caused by immune evasion of disseminated tumor cells (DTCs). In the skeleton, tumor cells not only disseminate to the bone marrow but also to osteogenic niches in which they interact with newly mineralizing bone extracellular matrix (ECM). However, it remains unclear how mineralization of collagen type I, the primary component of bone ECM, regulates tumor‐immune cell interactions. Here, a combination of synthetic bone matrix models with controlled mineral content, nanoscale optical imaging, and flow cytometry are utilized to evaluate how collagen type I mineralization affects the biochemical and biophysical properties of the tumor cell glycocalyx, a dense layer of glycosylated proteins and lipids decorating their cell surface. These results suggest that collagen mineralization upregulates mucin‐typeO‐glycosylation and sialylation by tumor cells, which increases their glycocalyx thickness while enhancing resistance to attack by natural killer (NK) cells. These changes are functionally linked as treatment with a sialylation inhibitor decreased mineralization‐dependent glycocalyx thickness and made tumor cells more susceptible to NK cell attack. Together, these results suggest that interference with glycocalyx sialylation may represent a therapeutic strategy to enhance cancer immunotherapies targeting bone‐metastatic breast cancer.
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In Situ Synthesis of an Aptamer‐Based Polyvalent Antibody Mimic on the Cell Surface for Enhanced Interactions between Immune and Cancer Cells
Abstract An ability to promote therapeutic immune cells to recognize cancer cells is important for the success of cell‐based cancer immunotherapy. We present a synthetic method for functionalizing the surface of natural killer (NK) cells with a supramolecular aptamer‐based polyvalent antibody mimic (PAM). The PAM is synthesized on the cell surface through nucleic acid assembly and hybridization. The data show that PAM has superiority over its monovalent counterpart in powering NKs to bind to cancer cells, and that PAM‐engineered NK cells exhibit the capability of killing cancer cells more effectively. Notably, aptamers can, in principle, be discovered against any cell receptors; moreover, the aptamers can be replaced by any other ligands when developing a PAM. Thus, this work has successfully demonstrated a technology platform for promoting interactions between immune and cancer cells.
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- PAR ID:
- 10151387
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 59
- Issue:
- 29
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 11892-11897
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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