Enhanced anti-tumor effects with microencapsulated c-myc antisense oligonucleotide.
A phosphorothioate c-myc antisense oligonucleotide was complexed with zinc and encapsulated into injectable biodegradable microspheres. The efficacy of this novel formulation was compared with intravenous administration of the unencapsulated drug in human melanoma and leukemia xenografts in immunocompromised mice. The microencapsulated formulation was more effective as shown by reduced tumor growth, a decreased number of metastases, reduced c-myc expression, and increased survival in the melanoma model, and decreased metastatic potential and increased survival in the leukemia model. These results show that, as has been demonstrated previously with protein and peptide drugs, greater therapeutic efficacy can be obtained when antisense oligonucleotides are delivered from sustained-release formulations.
Putney
S D
SD
Alkermes, Inc., Cambridge, MA 02139, USA.
Brown
J
J
Cucco
C
C
Lee
R
R
Skorski
T
T
Leonetti
C
C
Geiser
T
T
Calabretta
B
B
Zupi
G
G
Zon
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D017931:DNA Primers; D016259:Genes, myc; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D017931:DNA Primers; D016376:Oligonucleotides, Antisense