Influence of p53 on herpes simplex virus type 1 vectors for cancer gene therapy.
Herpes simplex virus type 1 (HSV 1) vectors are under investigation for use in gene therapy for colorectal cancer liver metastases. Approximately 60% of colorectal cancers possess p53 mutations, and p53 mutations can cause tumor cell resistance to radiation therapy and chemotherapy. p53 is also known to co-localize with at least one HSV 1 protein and influence HSV 1 gene expression. The purpose of this study was to determine if the loss or mutation of p53 in tumor cells alters the cytotoxicity of HSV 1 vectors. HSV 1 vector-mediated in vitro cytotoxicity assays were performed using stable transfectants of SAOS-2-LM2 cells and WiDr cells that express no p53, wild-type p53, mutant p53, or both wild-type p53 mutant p53. All stable transfectants were equally susceptible to HSV 1 vector cytotoxicity, and cell lines with mutant p53 were not resistant to HSV 1 vectors. These results provide additional rationale for the application of HSV 1 vector gene therapy for colorectal cancer.
Yoon
S S
SS
Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114, USA.
Carroll
N M
NM
Chiocca
E A
EA
Tanabe
K K
KK
D000818:Animals; D002522:Chlorocebus aethiops; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D014407:Tumor Cells, Cultured