An Aptamer for Broad Cancer Targeting and Therapy
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...
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doaj-16f7e71ed5de4946bffbcccb1ce297642020-11-25T04:02:57ZengMDPI AGCancers2072-66942020-10-01123217321710.3390/cancers12113217An Aptamer for Broad Cancer Targeting and TherapyBethany Powell Gray0Xirui Song1David S. Hsu2Christina Kratschmer3Matthew Levy4Ashley P. Barry5Bruce A. Sullenger6Department of Surgery, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Surgery, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medical Oncology, Duke Cancer Institute, Center for Genomics and Computational Biology, Duke University Medical Center, Durham, NC 27710, USADepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USAResearch and Development Division, b3 bio, Inc., Durham, NC 27709, USADepartment of Surgery, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USARecent 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.https://www.mdpi.com/2072-6694/12/11/3217aptameraptamer-drug conjugateaptamer highly toxic drug conjugatecancerdrug targeting |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bethany Powell Gray Xirui Song David S. Hsu Christina Kratschmer Matthew Levy Ashley P. Barry Bruce A. Sullenger |
spellingShingle |
Bethany Powell Gray Xirui Song David S. Hsu Christina Kratschmer Matthew Levy Ashley P. Barry Bruce A. Sullenger An Aptamer for Broad Cancer Targeting and Therapy Cancers aptamer aptamer-drug conjugate aptamer highly toxic drug conjugate cancer drug targeting |
author_facet |
Bethany Powell Gray Xirui Song David S. Hsu Christina Kratschmer Matthew Levy Ashley P. Barry Bruce A. Sullenger |
author_sort |
Bethany Powell Gray |
title |
An Aptamer for Broad Cancer Targeting and Therapy |
title_short |
An Aptamer for Broad Cancer Targeting and Therapy |
title_full |
An Aptamer for Broad Cancer Targeting and Therapy |
title_fullStr |
An Aptamer for Broad Cancer Targeting and Therapy |
title_full_unstemmed |
An Aptamer for Broad Cancer Targeting and Therapy |
title_sort |
aptamer for broad cancer targeting and therapy |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-10-01 |
description |
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. |
topic |
aptamer aptamer-drug conjugate aptamer highly toxic drug conjugate cancer drug targeting |
url |
https://www.mdpi.com/2072-6694/12/11/3217 |
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