Dendritic cells transduced with wild-type p53 gene elicit potent anti-tumour immune responses

Clin Exp Immunol. 1999 Aug;117(2):244-51. doi: 10.1046/j.1365-2249.1999.00913.x.

Abstract

In this study we have tested the concept of using wild-type p53 gene for immunotherapy of cancer. Dendritic cells (DC) were transduced with a human wild-type p53 containing recombinant adenovirus (Ad-p53). About a half of DC transduced with this virus expressed p53 protein by FACS analysis 48 h after infection. Mice immunized twice with Ad-p53 DC developed substantial cytotoxic T lymphocyte (CTL) responses against tumour cells expressing wild-type and different mutant human and murine p53 genes. Very low CTL responses were observed against target cells infected with control adenovirus (Ad-c). Immunization with Ad-p53 provided complete tumour protection in 85% of mice challenged with tumour cells expressing human mutant p53 and in 72.7% of mice challenged with tumour cells with murine mutant p53. Treatment with Ad-p53-transduced DC significantly slowed the growth of established tumours. Thus, DC transduced with wild-type p53 may be a promising new tool for the immunotherapy of cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology
  • Animals
  • Antineoplastic Agents / immunology*
  • Antineoplastic Agents / pharmacology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dendritic Cells / transplantation
  • Dose-Response Relationship, Immunologic
  • Female
  • Genes, p53 / immunology*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology
  • Humans
  • Immunotherapy, Adoptive / methods
  • Injections, Subcutaneous
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Neoplasm Transplantation
  • Sarcoma, Experimental / genetics
  • Sarcoma, Experimental / immunology
  • Sarcoma, Experimental / therapy
  • Transfection / immunology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cancer Vaccines