当前位置： SCI文献检索 > CANCER GENE THERAPY期刊下所有文献 > Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.

Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.

Abstract：

:p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was carried out in patients with metastatic melanoma or breast cancer with increased p53 protein immunoreactivity in pretreatment tumor biopsies. The biological activity of the injected wt p53 was assayed by reverse transcriptase-polymerase chain reaction in tumor tissue. A total of six (five melanoma and one breast adenocarcinoma) patients were treated at dose levels dependent upon tumor size/dose escalation sequence. Five of six patients became positive for the transfer of wt p53 into tumor tissue 2 days after injection of the vector. Of the four patients assayed, all developed anti-adenoviral antibodies. Adverse reactions associated with i.t. injection were mild, with no obvious correlation between the incidence, severity, or relationship of the events and drug dose. p53 gene therapy by i.t. injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective (with respect to transduction frequency) in patients with either metastatic melanoma or breast cancer.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Dummer R,Bergh J,Karlsson Y,Horowitz JA,Mulder NH,Huinink DTB,Burg G,Hofbauer G,Osanto S

doi

10.1038/sj.cgt.7700214

subject

Has Abstract

pub_date

2000-07-01 00:00:00

pages

1069-76

issue

7

eissn

0929-1903

issn

1476-5500

journal_volume

7

pub_type

临床试验,杂志文章,多中心研究

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