An Aptamer for Broad Cancer Targeting and Therapy
1
Department of Surgery, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA
2
Department of Medical Oncology, Duke Cancer Institute, Center for Genomics and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA
3
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
4
Research and Development Division, b3 bio, Inc., Durham, NC 27709, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(11), 3217; https://doi.org/10.3390/cancers12113217
Received: 1 October 2020 / Revised: 24 October 2020 / Accepted: 29 October 2020 / Published: 31 October 2020
(This article belongs to the Special Issue The Role of Aptamers in Cancer Diagnostics and Therapy)
Simple Summary
Recent efforts to improve chemotherapy’s antitumor effects have increasingly focused on targeted therapies, where the drug is modified with an agent able to specifically deliver it to the tumor while limiting its accumulation in normal tissue. Aptamers, comprised of short pieces of RNA or DNA, are ideal for this type of drug targeting due in part to their ease of chemical synthesis. The E3 aptamer was previously conjugated to highly toxic chemotherapeutics and shown to target and treat prostate tumors. Here, we show that E3 is not limited to prostate cancer targeting but appears to broadly target cancer cells. E3 highly toxic drug conjugates also efficiently kill a broad range of cancer types, and E3 targets tumors that closely model patient tumors. Thus, the E3 aptamer appears to be a general agent for specific delivery of chemotherapy to tumors and should improve antitumor treatment while reducing unwanted toxicities in other tissues.
Recent advances in chemotherapy treatments are increasingly targeted therapies, with the drug conjugated to an antibody able to deliver it directly to the tumor. As high-affinity chemical ligands that are much smaller in size, aptamers are ideal for this type of drug targeting. Aptamer-highly toxic drug conjugates (ApTDCs) based on the E3 aptamer, selected on prostate cancer cells, target and inhibit prostate tumor growth in vivo. Here, we observe that E3 also broadly targets numerous other cancer types, apparently representing a universal aptamer for cancer targeting. Accordingly, ApTDCs formed by conjugation of E3 to the drugs monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF) efficiently target and kill a range of different cancer cells. Notably, this targeting extends to both patient-derived explant (PDX) cancer cell lines and tumors, with the E3 MMAE and MMAF conjugates inhibiting PDX cell growth in vitro and with the E3 aptamer targeting PDX colorectal tumors in vivo.
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Keywords:
aptamer; aptamer-drug conjugate; aptamer highly toxic drug conjugate; cancer; drug targeting
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style
Powell Gray, B.; Song, X.; Hsu, D.S.; Kratschmer, C.; Levy, M.; Barry, A.P.; Sullenger, B.A. An Aptamer for Broad Cancer Targeting and Therapy. Cancers 2020, 12, 3217. https://doi.org/10.3390/cancers12113217
AMA Style
Powell Gray B, Song X, Hsu DS, Kratschmer C, Levy M, Barry AP, Sullenger BA. An Aptamer for Broad Cancer Targeting and Therapy. Cancers. 2020; 12(11):3217. https://doi.org/10.3390/cancers12113217
Chicago/Turabian StylePowell Gray, Bethany; Song, Xirui; Hsu, David S.; Kratschmer, Christina; Levy, Matthew; Barry, Ashley P.; Sullenger, Bruce A. 2020. "An Aptamer for Broad Cancer Targeting and Therapy" Cancers 12, no. 11: 3217. https://doi.org/10.3390/cancers12113217
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