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Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers
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 mechanis...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775132/ https://www.ncbi.nlm.nih.gov/pubmed/35052426 http://dx.doi.org/10.3390/genes13010086 |
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author | Mallik, Prabhat K. Nishikawa, Kimi Mallik, Pramit Shi, Hua |
author_facet | Mallik, Prabhat K. Nishikawa, Kimi Mallik, Pramit Shi, Hua |
author_sort | Mallik, Prabhat K. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8775132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87751322022-01-21 Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers Mallik, Prabhat K. Nishikawa, Kimi Mallik, Pramit Shi, Hua Genes (Basel) Article 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. MDPI 2021-12-29 /pmc/articles/PMC8775132/ /pubmed/35052426 http://dx.doi.org/10.3390/genes13010086 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mallik, Prabhat K. Nishikawa, Kimi Mallik, Pramit Shi, Hua Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers |
title | Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers |
title_full | Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers |
title_fullStr | Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers |
title_full_unstemmed | Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers |
title_short | Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers |
title_sort | complement-mediated selective tumor cell lysis enabled by bi-functional rna aptamers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775132/ https://www.ncbi.nlm.nih.gov/pubmed/35052426 http://dx.doi.org/10.3390/genes13010086 |
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