Oncolytic potential of E1B 55 kDa-deleted YKL-1 recombinant adenovirus: correlation with p53 functional status.
YKL-1, E1B 55 kDa-deleted recombinant adenovirus vector, capable of harboring a transgene casette of up to 4.9 kb, was newly constructed by reintroducing E1A and E1B 19 kDa into E1/E3-deleted adenoviral vector with a homologous recombination in E. coli. Virus replication and cytotoxicity were dramatically attenuated in all 3 different types of normal human cells. In contrast, YKL-1 efficiently replicated and induced cytotoxicity in most cancer cells, especially Hep3B and C33A cells with an inactivating p53 mutation. However, both H460 and HepG2 exhibited intermediate sensitivity to YKL-1, which was between that of Hep3B or C33A and normal human cells. The YKL-1 and DNA damaging agent, camptothecin effectively induced p53 in H460 and HepG2 as well as in normal cells. Furthermore, YKL-1 effectively prohibited both Hep3B and C33A tumor growth in nu/nu mice in a dose-dependent manner. H/E staining and TUNEL assay indicated a largely distributed necrotic area and apoptosis on its periphery. This study, therefore, indicates that YKL-1, possesses promising potential as an oncolytic adenoviral vector, which acts partially in a p53-dependent manner.
Lee
H
H
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Kim
J
J
Lee
B
B
Chang
J W
JW
Ahn
J
J
Park
J O
JO
Choi
J
J
Yun
C O
CO
Kim
B S
BS
Kim
J H
JH
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D011995:Recombination, Genetic; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014779:Virus Replication
D017501:Adenovirus E1B Proteins; D016159:Tumor Suppressor Protein p53