Enhanced tumor suppressor gene therapy via replication-deficient adenovirus vectors expressing an N-terminal truncated retinoblastoma protein.
The preclinical studies presented here demonstrate that treatment of human non-small cell lung carcinoma and bladder carcinoma cells by a recombinant adenovirus vector, AdCMVpRB94, expressing the N-terminal truncated retinoblastoma (RB) protein (pRB94) completely suppressed the tumorigenicity of the treated tumor cells in nude mice. Furthermore, gene therapy of established human RB- and RB+ bladder xenograft cancers in nude mice by AdCMVpRB94 resulted in regression of the treated tumors. Of note, although both the full-length and the truncated forms of the RB protein, when overexpressed in tumor cells via replication-deficient adenovirus vectors, were capable of suppression of tumor growth, the pRB94 was evidently more potent than the full-length RB protein.
Xu
H J
HJ
Department of Molecular Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Zhou
Y
Y
Seigne
J
J
Perng
G S
GS
Mixon
M
M
Zhang
C
C
Li
J
J
Benedict
W F
WF
Hu
S X
SX
D000260:Adenoviruses, Human / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000628:therapy*; D004261:DNA Replication; D018076:DNA, Complementary / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics* / Q000502:physiology; D016161:Genes, Retinoblastoma; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*; D014779:Virus Replication
D018076:DNA, Complementary; D010446:Peptide Fragments; D016160:Retinoblastoma Protein