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Clin Exp Immunol ; 117(2): 244-51, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10444254

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.


Subject(s)
Antineoplastic Agents/immunology , Cancer Vaccines/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Genes, p53/immunology , Transfection/immunology , Adenoviruses, Human/genetics , Adenoviruses, Human/immunology , Animals , Antineoplastic Agents/pharmacology , Cancer Vaccines/administration & dosage , Cancer Vaccines/genetics , Dendritic Cells/transplantation , Dose-Response Relationship, Immunologic , Female , 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 , Tumor Cells, Cultured
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