Combination of Adoptive Immunotherapy with Herceptin for Patients with HER2-expressing Breast Cancer

Makoto Kubo, Takashi Morisaki, Hideo Kuroki, Akira Tasaki, Naoki Yamanaka, Kotaro Matsumoto, Katsuya Nakamura, Hideya Ohnishi, Eishi Baba, Mitsuo Katano

研究成果: ジャーナルへの寄稿記事

29 引用 (Scopus)

抄録

Clinical use of Herceptin (trastuzumab), which is a humanized monoclonal antibody against HER2, started for patients with HER2-overexpressing breast cancer. To potentiate the efficacy of the Herceptin therapy, this study focused on the combination of Herceptin with activated immune lymphocytes. We used peripheral blood mononuclear cells (PBMCs) as effector cells and used HER2-unexpressing K562 cells, HER2-weakly-expressing breast carcinoma cells (Breast-M), or HER2-strongly-expressing breast carcinoma cells (BT-474) as target cells. Interleukin-2 (IL-2)-activated PBMCs, IL-2/OKT-3-activated PBMCs and a streptococcal preparation OK-432-activated PBMCs were generated and used as effector cells. Cytotoxic activity was determined with 4-hour 51 Cr release assay. Both fresh PBMCs and activated PBMCs exhibited Herceptin-dependent cytotoxicity. Importantly, Herceptin-dependent cytotoxicity was found even at a lower effector to target cell ratio (E/T ratio) than that of Herceptin-independent cytotoxicity. In addition, Herceptin-dependent cytotoxicity by these activated PBMCs was observed even in HER2-weakly-expressing Breast-M cells. Since γ-globulin or anti-CD16 antibody abrogated Herceptin-dependent cytotoxicity, it seems likely that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the Herceptin-dependent cytotoxicity. We present a recurrent breast cancer patient with malignant pleural effusion, in which HER2-strongly-expressing tumor cells were present, who was undergoing Herceptin therapy. Cluster formation between tumor cells and intrapleural mononuclear cells was induced 24 hours after intravenous injection of Herceptin (4 mg/kg). Mononuclear cells bound specifically to HER2-strongly-expressing tumor cells but not to other cells, such as mesothelial cells, suggested a Herceptin-mediated binding like ADCC in vivo. Taken together, these findings suggest that the combination of Herceptin with various types of activated lymphocytes may be a new therapeutic strategy, not only for HER2-strongly-expressing breast cancer but also for HER2-weakly-expressing cancer.

元の言語英語
ページ(範囲)4443-4449
ページ数7
ジャーナルAnticancer research
23
発行部数6 A
出版物ステータス出版済み - 11 1 2003

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Adoptive Immunotherapy
Breast Neoplasms
Blood Cells
Trastuzumab
Interleukin-2
Neoplasms
Breast
Lymphocytes
Picibanil
Malignant Pleural Effusion
Antibodies, Monoclonal, Humanized
K562 Cells
Antibodies
Globulins
Intravenous Injections

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Kubo, M., Morisaki, T., Kuroki, H., Tasaki, A., Yamanaka, N., Matsumoto, K., ... Katano, M. (2003). Combination of Adoptive Immunotherapy with Herceptin for Patients with HER2-expressing Breast Cancer. Anticancer research, 23(6 A), 4443-4449.

Combination of Adoptive Immunotherapy with Herceptin for Patients with HER2-expressing Breast Cancer. / Kubo, Makoto; Morisaki, Takashi; Kuroki, Hideo; Tasaki, Akira; Yamanaka, Naoki; Matsumoto, Kotaro; Nakamura, Katsuya; Ohnishi, Hideya; Baba, Eishi; Katano, Mitsuo.

:: Anticancer research, 巻 23, 番号 6 A, 01.11.2003, p. 4443-4449.

研究成果: ジャーナルへの寄稿記事

Kubo, M, Morisaki, T, Kuroki, H, Tasaki, A, Yamanaka, N, Matsumoto, K, Nakamura, K, Ohnishi, H, Baba, E & Katano, M 2003, 'Combination of Adoptive Immunotherapy with Herceptin for Patients with HER2-expressing Breast Cancer', Anticancer research, 巻. 23, 番号 6 A, pp. 4443-4449.
Kubo M, Morisaki T, Kuroki H, Tasaki A, Yamanaka N, Matsumoto K その他. Combination of Adoptive Immunotherapy with Herceptin for Patients with HER2-expressing Breast Cancer. Anticancer research. 2003 11 1;23(6 A):4443-4449.
Kubo, Makoto ; Morisaki, Takashi ; Kuroki, Hideo ; Tasaki, Akira ; Yamanaka, Naoki ; Matsumoto, Kotaro ; Nakamura, Katsuya ; Ohnishi, Hideya ; Baba, Eishi ; Katano, Mitsuo. / Combination of Adoptive Immunotherapy with Herceptin for Patients with HER2-expressing Breast Cancer. :: Anticancer research. 2003 ; 巻 23, 番号 6 A. pp. 4443-4449.
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title = "Combination of Adoptive Immunotherapy with Herceptin for Patients with HER2-expressing Breast Cancer",
abstract = "Clinical use of Herceptin (trastuzumab), which is a humanized monoclonal antibody against HER2, started for patients with HER2-overexpressing breast cancer. To potentiate the efficacy of the Herceptin therapy, this study focused on the combination of Herceptin with activated immune lymphocytes. We used peripheral blood mononuclear cells (PBMCs) as effector cells and used HER2-unexpressing K562 cells, HER2-weakly-expressing breast carcinoma cells (Breast-M), or HER2-strongly-expressing breast carcinoma cells (BT-474) as target cells. Interleukin-2 (IL-2)-activated PBMCs, IL-2/OKT-3-activated PBMCs and a streptococcal preparation OK-432-activated PBMCs were generated and used as effector cells. Cytotoxic activity was determined with 4-hour 51 Cr release assay. Both fresh PBMCs and activated PBMCs exhibited Herceptin-dependent cytotoxicity. Importantly, Herceptin-dependent cytotoxicity was found even at a lower effector to target cell ratio (E/T ratio) than that of Herceptin-independent cytotoxicity. In addition, Herceptin-dependent cytotoxicity by these activated PBMCs was observed even in HER2-weakly-expressing Breast-M cells. Since γ-globulin or anti-CD16 antibody abrogated Herceptin-dependent cytotoxicity, it seems likely that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the Herceptin-dependent cytotoxicity. We present a recurrent breast cancer patient with malignant pleural effusion, in which HER2-strongly-expressing tumor cells were present, who was undergoing Herceptin therapy. Cluster formation between tumor cells and intrapleural mononuclear cells was induced 24 hours after intravenous injection of Herceptin (4 mg/kg). Mononuclear cells bound specifically to HER2-strongly-expressing tumor cells but not to other cells, such as mesothelial cells, suggested a Herceptin-mediated binding like ADCC in vivo. Taken together, these findings suggest that the combination of Herceptin with various types of activated lymphocytes may be a new therapeutic strategy, not only for HER2-strongly-expressing breast cancer but also for HER2-weakly-expressing cancer.",
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T1 - Combination of Adoptive Immunotherapy with Herceptin for Patients with HER2-expressing Breast Cancer

AU - Kubo, Makoto

AU - Morisaki, Takashi

AU - Kuroki, Hideo

AU - Tasaki, Akira

AU - Yamanaka, Naoki

AU - Matsumoto, Kotaro

AU - Nakamura, Katsuya

AU - Ohnishi, Hideya

AU - Baba, Eishi

AU - Katano, Mitsuo

PY - 2003/11/1

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N2 - Clinical use of Herceptin (trastuzumab), which is a humanized monoclonal antibody against HER2, started for patients with HER2-overexpressing breast cancer. To potentiate the efficacy of the Herceptin therapy, this study focused on the combination of Herceptin with activated immune lymphocytes. We used peripheral blood mononuclear cells (PBMCs) as effector cells and used HER2-unexpressing K562 cells, HER2-weakly-expressing breast carcinoma cells (Breast-M), or HER2-strongly-expressing breast carcinoma cells (BT-474) as target cells. Interleukin-2 (IL-2)-activated PBMCs, IL-2/OKT-3-activated PBMCs and a streptococcal preparation OK-432-activated PBMCs were generated and used as effector cells. Cytotoxic activity was determined with 4-hour 51 Cr release assay. Both fresh PBMCs and activated PBMCs exhibited Herceptin-dependent cytotoxicity. Importantly, Herceptin-dependent cytotoxicity was found even at a lower effector to target cell ratio (E/T ratio) than that of Herceptin-independent cytotoxicity. In addition, Herceptin-dependent cytotoxicity by these activated PBMCs was observed even in HER2-weakly-expressing Breast-M cells. Since γ-globulin or anti-CD16 antibody abrogated Herceptin-dependent cytotoxicity, it seems likely that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the Herceptin-dependent cytotoxicity. We present a recurrent breast cancer patient with malignant pleural effusion, in which HER2-strongly-expressing tumor cells were present, who was undergoing Herceptin therapy. Cluster formation between tumor cells and intrapleural mononuclear cells was induced 24 hours after intravenous injection of Herceptin (4 mg/kg). Mononuclear cells bound specifically to HER2-strongly-expressing tumor cells but not to other cells, such as mesothelial cells, suggested a Herceptin-mediated binding like ADCC in vivo. Taken together, these findings suggest that the combination of Herceptin with various types of activated lymphocytes may be a new therapeutic strategy, not only for HER2-strongly-expressing breast cancer but also for HER2-weakly-expressing cancer.

AB - Clinical use of Herceptin (trastuzumab), which is a humanized monoclonal antibody against HER2, started for patients with HER2-overexpressing breast cancer. To potentiate the efficacy of the Herceptin therapy, this study focused on the combination of Herceptin with activated immune lymphocytes. We used peripheral blood mononuclear cells (PBMCs) as effector cells and used HER2-unexpressing K562 cells, HER2-weakly-expressing breast carcinoma cells (Breast-M), or HER2-strongly-expressing breast carcinoma cells (BT-474) as target cells. Interleukin-2 (IL-2)-activated PBMCs, IL-2/OKT-3-activated PBMCs and a streptococcal preparation OK-432-activated PBMCs were generated and used as effector cells. Cytotoxic activity was determined with 4-hour 51 Cr release assay. Both fresh PBMCs and activated PBMCs exhibited Herceptin-dependent cytotoxicity. Importantly, Herceptin-dependent cytotoxicity was found even at a lower effector to target cell ratio (E/T ratio) than that of Herceptin-independent cytotoxicity. In addition, Herceptin-dependent cytotoxicity by these activated PBMCs was observed even in HER2-weakly-expressing Breast-M cells. Since γ-globulin or anti-CD16 antibody abrogated Herceptin-dependent cytotoxicity, it seems likely that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the Herceptin-dependent cytotoxicity. We present a recurrent breast cancer patient with malignant pleural effusion, in which HER2-strongly-expressing tumor cells were present, who was undergoing Herceptin therapy. Cluster formation between tumor cells and intrapleural mononuclear cells was induced 24 hours after intravenous injection of Herceptin (4 mg/kg). Mononuclear cells bound specifically to HER2-strongly-expressing tumor cells but not to other cells, such as mesothelial cells, suggested a Herceptin-mediated binding like ADCC in vivo. Taken together, these findings suggest that the combination of Herceptin with various types of activated lymphocytes may be a new therapeutic strategy, not only for HER2-strongly-expressing breast cancer but also for HER2-weakly-expressing cancer.

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