TY - JOUR
T1 - An aptamer for broad cancer targeting and therapy
AU - Gray, Bethany Powell
AU - Song, Xirui
AU - Hsu, David S.
AU - Kratschmer, Christina
AU - Levy, Matthew
AU - Barry, Ashley P.
AU - Sullenger, Bruce A.
N1 - Funding Information:
Funding: This research was funded by the Department of Defense (DoD) Prostate Cancer Research Program (PCRP) Postdoctoral Training Award PC131874 (to B.P.G.), PCRP Idea Development Award PC190428 (to B.P.G.) and Synergistic Idea Award PC111812P2/W81XWH-12-1-0262 (to B.A.S.); Stand Up to Cancer Innovative Research Grant SU2C-AACR-IRG-0809 (to M.L.); and National Cancer Institute (NCI) Grants R21CA182330 (to M.L.) and R21CA157366-03 (to M.L.). Additionally, this work was supported by Duke Cancer Institute (DCI) NCI Grant P30-CA014236 funding for the Duke Optical Molecular Imaging and Analysis Facility (in vivo imaging) and the Duke Light Microscopy Core Facility (confocal microscopy).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Aptamer
KW - Aptamer highly toxic drug conjugate
KW - Aptamer-drug conjugate
KW - Cancer
KW - Drug targeting
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U2 - 10.3390/cancers12113217
DO - 10.3390/cancers12113217
M3 - Article
AN - SCOPUS:85094862352
SN - 2072-6694
VL - 12
SP - 1
EP - 18
JO - Cancers
JF - Cancers
IS - 11
M1 - 3217
ER -