Antitumor effect of intratumoral administration of bone marrow-derived dendritic cells transduced with wild-type p53 gene

Takayoshi Murakami, Naoyuki Tokunaga, Toshihiko Waku, Shinya Gomi, Shunsuke Kagawa, Noriaki Tanaka, Toshiyoshi Fujiwara

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Purpose: Dendritic cells (DCs) are attractive effectors for cancer immunotherapy because of their potential to function as professional antigen-presenting cells for initiating cellular immune responses. The tumor suppressor gene p53 is pivotal in the regulation of apoptosis, and ∼50% of human malignancies exhibit mutation and aberrant expression of p53. We investigated the antitumor effect of intratumoral administration of bone marrow-derived dendritic cells transduced with wild-type p53 gene. Experimental Design: We examined whether intratumoral administration of DCs infected with recombinant adenovirus expressing murine wild-type p53 (Ad-mp53) could induce systemic antitumor responses against mutant p53-expressing tumors, highly immunogenic MethA, or weakly immunogenic MCA-207 implanted in syngeneic mice. Results: Accumulation of wild-type p53 protein in bone marrow-derived murine DCs could he successfully achieved by Ad-mp53 infection. Treatment with intratumoral injection of Ad-mp53-transduced DCs caused a marked reduction in the in vivo growth of established MethA and MCA-207 tumors with massive cellular infiltrates. Administration of p53-expressing DCs suppressed the growth of both injected MCA-207 tumors and untreated distant MCA-207 tumors, but not unrelated Lewis lung carcinoma tumors, suggesting the augmentation of systemic immunogenicity against MCA-207 tumor cells. Moreover, intratumoral injection of p53-expressing DCs had a greater antitumor effect than did s.c. immunization. Conclusions: Our results indicate that intratumoral administration of DCs expressing murine wild-type p53 leads to significant systemic immune responses and potent antitumor effects in mutant p53-expressing murine cancer models. These findings raise the possibility of using this strategy of intratumoral injection of p53-expressing DCs for human cancer treatment.

Original languageEnglish
Pages (from-to)3871-3880
Number of pages10
JournalClinical Cancer Research
Volume10
Issue number11
DOIs
Publication statusPublished - Jun 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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