Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers

Authors

Hua Shi, University at Albany, State University of New YorkFollow
Prabhat K. Mallik, University at Albany, State University of New York
Kimi Nishikawa, University at Albany, State University of New York
Pramit Mallik, University at Albany, State University of New York

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Document Type

Article

Publication Date

12-29-2021

DOI

https://doi.org/10.3390/genes13010086

Abstract

Unlike microbes that infect the human body, cancer cells are descended from normal cells and are not easily recognizable as “foreign” by the immune system of the host. However, if the malignant cells can be specifically earmarked for attack by a synthetic “designator”, the powerful effector mechanisms of the immune response can be conscripted to treat cancer. To implement this strategy, we have been developing aptamer-derived molecular adaptors to invoke synthetic immune responses against cancer cells. Here we describe multi-valent aptamers that simultaneously bind target molecules on the surface of cancer cells and an activated complement protein, which would tag the target molecules and their associated cells as “foreign” and trigger multiple effector mechanisms. Increased deposition of the complement proteins on the surface of cancer cells via aptamer binding to membrane targets could induce the formation of the membrane attack complex or cytotoxic degranulation by phagocytes and natural killer cells, thereby causing irreversible destruction of the targeted cells. Specifically, we designed and constructed a bi-functional aptamer linking EGFR and C3b/iC3b, and used it in a cell-based assay to cause lysis of MDA-MB-231 and BT-20 breast cancer cells, with either human or mouse serum as the source of complement factors.

Comments

This is the Publisher’s PDF of the following article made available by Genes: Mallik PK, Nishikawa K, Mallik P, Shi H. Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers. Genes. 2022; 13(1):86. https://doi.org/10.3390/genes13010086

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Shi, Hua; Mallik, Prabhat K.; Nishikawa, Kimi; and Mallik, Pramit, "Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers" (2021). Biological Sciences Faculty Scholarship. 13.
https://scholarsarchive.library.albany.edu/biology_fac_scholar/13