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Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene
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| Zeitschriftentitel: | Clinical Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | Clinical Cancer Research, 10, 2004, 11, S. 3871-3880 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Murakami, Takayoshi Tokunaga, Naoyuki Waku, Toshihiko Gomi, Shinya Kagawa, Shunsuke Tanaka, Noriaki Fujiwara, Toshiyoshi Murakami, Takayoshi Tokunaga, Naoyuki Waku, Toshihiko Gomi, Shinya Kagawa, Shunsuke Tanaka, Noriaki Fujiwara, Toshiyoshi |
|---|---|
| author |
Murakami, Takayoshi Tokunaga, Naoyuki Waku, Toshihiko Gomi, Shinya Kagawa, Shunsuke Tanaka, Noriaki Fujiwara, Toshiyoshi |
| spellingShingle |
Murakami, Takayoshi Tokunaga, Naoyuki Waku, Toshihiko Gomi, Shinya Kagawa, Shunsuke Tanaka, Noriaki Fujiwara, Toshiyoshi Clinical Cancer Research Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene Cancer Research Oncology |
| author_sort |
murakami, takayoshi |
| spelling |
Murakami, Takayoshi Tokunaga, Naoyuki Waku, Toshihiko Gomi, Shinya Kagawa, Shunsuke Tanaka, Noriaki Fujiwara, Toshiyoshi 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-03-0599 <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>Results: Accumulation of wild-type p53 protein in bone marrow-derived murine DCs could be 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.</jats:p> <jats:p>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.</jats:p> Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type <b> <i>p53</i> </b> Gene Clinical Cancer Research |
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10.1158/1078-0432.ccr-03-0599 |
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American Association for Cancer Research (AACR), 2004 |
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American Association for Cancer Research (AACR), 2004 |
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1078-0432 1557-3265 |
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Clinical Cancer Research |
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49 |
| title |
Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_unstemmed |
Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_full |
Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_fullStr |
Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_full_unstemmed |
Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_short |
Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_sort |
antitumor effect of intratumoral administration of bone marrow-derived dendritic cells transduced with wild-type <b>
<i>p53</i>
</b> gene |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1078-0432.ccr-03-0599 |
| publishDate |
2004 |
| physical |
3871-3880 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>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.</jats:p>
<jats:p>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.</jats:p>
<jats:p>Results: Accumulation of wild-type p53 protein in bone marrow-derived murine DCs could be 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.</jats:p>
<jats:p>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.</jats:p> |
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| _version_ | 1792335739253424130 |
| author | Murakami, Takayoshi, Tokunaga, Naoyuki, Waku, Toshihiko, Gomi, Shinya, Kagawa, Shunsuke, Tanaka, Noriaki, Fujiwara, Toshiyoshi |
| author_facet | Murakami, Takayoshi, Tokunaga, Naoyuki, Waku, Toshihiko, Gomi, Shinya, Kagawa, Shunsuke, Tanaka, Noriaki, Fujiwara, Toshiyoshi, Murakami, Takayoshi, Tokunaga, Naoyuki, Waku, Toshihiko, Gomi, Shinya, Kagawa, Shunsuke, Tanaka, Noriaki, Fujiwara, Toshiyoshi |
| author_sort | murakami, takayoshi |
| container_issue | 11 |
| container_start_page | 3871 |
| container_title | Clinical Cancer Research |
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| description | <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>Results: Accumulation of wild-type p53 protein in bone marrow-derived murine DCs could be 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.</jats:p> <jats:p>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.</jats:p> |
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| imprint | American Association for Cancer Research (AACR), 2004 |
| imprint_str_mv | American Association for Cancer Research (AACR), 2004 |
| institution | DE-Zwi2, DE-D161, DE-Zi4, DE-Gla1, DE-15, DE-Pl11, DE-Rs1, DE-14, DE-105, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1 |
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| publishDate | 2004 |
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| spelling | Murakami, Takayoshi Tokunaga, Naoyuki Waku, Toshihiko Gomi, Shinya Kagawa, Shunsuke Tanaka, Noriaki Fujiwara, Toshiyoshi 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-03-0599 <jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>Results: Accumulation of wild-type p53 protein in bone marrow-derived murine DCs could be 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.</jats:p> <jats:p>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.</jats:p> Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type <b> <i>p53</i> </b> Gene Clinical Cancer Research |
| spellingShingle | Murakami, Takayoshi, Tokunaga, Naoyuki, Waku, Toshihiko, Gomi, Shinya, Kagawa, Shunsuke, Tanaka, Noriaki, Fujiwara, Toshiyoshi, Clinical Cancer Research, Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene, Cancer Research, Oncology |
| title | Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_full | Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_fullStr | Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_full_unstemmed | Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_short | Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| title_sort | antitumor effect of intratumoral administration of bone marrow-derived dendritic cells transduced with wild-type <b> <i>p53</i> </b> gene |
| title_unstemmed | Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type p53 Gene |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1078-0432.ccr-03-0599 |