Gene therapy for non-small cell lung cancer: a preliminary report of a phase I trial of adenoviral p53 gene replacement.
The identification of genetic lesions that lead a normal cell to become malignant presents us with the opportunity of targeting those lesions as a means of therapy. Given the key role played by the tumor suppressor gene p53 in cell cycle regulation and apoptosis, and the evidence linking p53 mutations with non-small cell lung cancer, attempts at p53 replacement are a logical approach to therapy in this disease. In a phase I study, administration of an adenoviral p53 vector (Adp53) to 21 patients with advanced non-small cell lung cancer produced little toxicity. Up to six intratumoral injections at monthly intervals were well-tolerated. Expression of the p53 transgene was evident, along with potentially useful clinical responses. Time to disease progression in the indicator lesion treated with Adp53 appears to be enhanced by higher doses of vector, concomitant cisplatin therapy, and evidence of apoptosis on tumor biopsy specimens. Phase II trials should now be undertaken to determine the response rate to Adp53.
Roth
J A
JA
Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Swisher
S G
SG
Merritt
J A
JA
Lawrence
D D
DD
Kemp
B L
BL
Carrasco
C H
CH
El-Naggar
A K
AK
Fossella
F V
FV
Glisson
B S
BS
Hong
W K
WK
Khurl
F R
FR
Kurie
J M
JM
Nesbitt
J C
JC
Pisters
K
K
Putnam
J B
JB
Schrump
D S
DS
Shin
D M
DM
Walsh
G L
GL
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000914:Antibodies, Viral / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D018014:Gene Transfer Techniques; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*
D000914:Antibodies, Viral