Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells
Cytokine-Induced Killer (CIK) cells share several functional and phenotypical properties of both T and natural killer (NK) cells. They represent an attractive approach for cell-based immunotherapy, as they do not require antigen-specific priming for tumor cell recognition, and can be rapidly expande...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-01-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2020.1777046 |
| _version_ | 1818721565894770688 |
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| author | Roberta Sommaggio Elisa Cappuzzello Anna Dalla Pietà Anna Tosi Pierangela Palmerini Debora Carpanese Lorenzo Nicolè Antonio Rosato |
| author_facet | Roberta Sommaggio Elisa Cappuzzello Anna Dalla Pietà Anna Tosi Pierangela Palmerini Debora Carpanese Lorenzo Nicolè Antonio Rosato |
| author_sort | Roberta Sommaggio |
| collection | DOAJ |
| description | Cytokine-Induced Killer (CIK) cells share several functional and phenotypical properties of both T and natural killer (NK) cells. They represent an attractive approach for cell-based immunotherapy, as they do not require antigen-specific priming for tumor cell recognition, and can be rapidly expanded in vitro. Their relevant expression of FcγRIIIa (CD16a) can be exploited in combination with clinical-grade monoclonal antibodies (mAbs) to redirect their lytic activity in an antigen-specific manner. Here, we report the efficacy of this combined approach against triple negative breast cancer (TNBC), an aggressive tumor that still requires therapeutic options. Different primitive and metastatic TNBC cancer mouse models were established in NSG mice, either by implanting patient-derived TNBC samples or injecting MDA-MB-231 cells orthotopically or intravenously. The combined treatment consisted in the repeated intratumoral or intravenous injection of CIK cells and cetuximab. Tumor growth and metastasis were monitored by bioluminescence or immunohistochemistry, and survival was recorded. CIK cells plus cetuximab significantly restrained primitive tumor growth in mice, either in patient-derived tumor xenografts or MDA-MB-231 cell line models. Moreover, this approach almost completely abolished metastasis spreading and dramatically improved survival. The antigen-specific mAb favored tumor and metastasis tissue infiltration by CIK cells, and led to an enrichment of the CD16a+ subset. Data highlight the potentiality of this novel immunotherapy strategy where a nonspecific cytotoxic cell population can be converted into tumor-specific effectors with clinical-grade antibodies, thus providing not only a therapeutic option for TNBC but also a valid alternative to more complex approaches based on chimeric antigen receptor-engineered cells. List of abbreviations ACT, Adoptive Cell Transfer; ADCC, Antibody-Dependent Cell-mediated Cytotoxicity; ADP, Adenosine diphosphate; BLI, Bioluminescence Imaging; CAR, Chimeric Antigen Receptor; CIK, Cytokine Induced Killer cells; CTX, Cetuximab; DMEM, Dulbecco’s Modified Eagle Medium; EGFR, Human Epidermal Growth Factor 1; ER, Estrogen; FBS, Fetal Bovine Serum; FFPE, Formalin-Fixed Paraffin-Embedded; GMP, Good Manufacturing Practices; GVHD, Graft Versus Host Disease; HER2, Human Epidermal Growth Factor 2; HRP, Horseradish Peroxidase; IFN-γ, Interferon-γ; IHC, Immunohistochemistry; IL-2, Interleukin-2; ISO, Irrelevant antibody; i.t., intratumoral; i.v., intravenous, mAbs, Monoclonal Antibodies; mIHC, Multiplex Fluorescence Immunohistochemistry; MHC, Major Histocompatibility Complex; NK, Natural Killer; NKG2D, Natural-Killer group 2 member D; NSG, NOD/SCID common γ chain knockout; PARP, Poly ADP-ribose polymerase; PBMCs, Peripheral Blood Mononuclear Cells; PBS, Phosphate-buffered saline; PDX, Patient-derived xenograft; PR, Progesterone; rhIFN-γ, Recombinant Human Interferon-γ; RPMI, Roswell Park Memorial Institute; STR, Short tandem Repeat; TCR, T Cell Receptor; TNBC, Triple Negative Breast Cancer; TSA, Tyramide Signal Amplification |
| first_indexed | 2024-12-17T20:40:46Z |
| format | Article |
| id | doaj.art-eebe901439664a3eb3794810f138b09f |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-17T20:40:46Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-eebe901439664a3eb3794810f138b09f2022-12-21T21:33:20ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.17770461777046Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cellsRoberta Sommaggio0Elisa Cappuzzello1Anna Dalla Pietà2Anna Tosi3Pierangela Palmerini4Debora Carpanese5Lorenzo Nicolè6Antonio Rosato7Veneto Institute of Oncology IOV – IRCCSUniversity of PaduaUniversity of PaduaUniversity of PaduaUniversity of PaduaVeneto Institute of Oncology IOV – IRCCSUniversity of PaduaVeneto Institute of Oncology IOV – IRCCSCytokine-Induced Killer (CIK) cells share several functional and phenotypical properties of both T and natural killer (NK) cells. They represent an attractive approach for cell-based immunotherapy, as they do not require antigen-specific priming for tumor cell recognition, and can be rapidly expanded in vitro. Their relevant expression of FcγRIIIa (CD16a) can be exploited in combination with clinical-grade monoclonal antibodies (mAbs) to redirect their lytic activity in an antigen-specific manner. Here, we report the efficacy of this combined approach against triple negative breast cancer (TNBC), an aggressive tumor that still requires therapeutic options. Different primitive and metastatic TNBC cancer mouse models were established in NSG mice, either by implanting patient-derived TNBC samples or injecting MDA-MB-231 cells orthotopically or intravenously. The combined treatment consisted in the repeated intratumoral or intravenous injection of CIK cells and cetuximab. Tumor growth and metastasis were monitored by bioluminescence or immunohistochemistry, and survival was recorded. CIK cells plus cetuximab significantly restrained primitive tumor growth in mice, either in patient-derived tumor xenografts or MDA-MB-231 cell line models. Moreover, this approach almost completely abolished metastasis spreading and dramatically improved survival. The antigen-specific mAb favored tumor and metastasis tissue infiltration by CIK cells, and led to an enrichment of the CD16a+ subset. Data highlight the potentiality of this novel immunotherapy strategy where a nonspecific cytotoxic cell population can be converted into tumor-specific effectors with clinical-grade antibodies, thus providing not only a therapeutic option for TNBC but also a valid alternative to more complex approaches based on chimeric antigen receptor-engineered cells. List of abbreviations ACT, Adoptive Cell Transfer; ADCC, Antibody-Dependent Cell-mediated Cytotoxicity; ADP, Adenosine diphosphate; BLI, Bioluminescence Imaging; CAR, Chimeric Antigen Receptor; CIK, Cytokine Induced Killer cells; CTX, Cetuximab; DMEM, Dulbecco’s Modified Eagle Medium; EGFR, Human Epidermal Growth Factor 1; ER, Estrogen; FBS, Fetal Bovine Serum; FFPE, Formalin-Fixed Paraffin-Embedded; GMP, Good Manufacturing Practices; GVHD, Graft Versus Host Disease; HER2, Human Epidermal Growth Factor 2; HRP, Horseradish Peroxidase; IFN-γ, Interferon-γ; IHC, Immunohistochemistry; IL-2, Interleukin-2; ISO, Irrelevant antibody; i.t., intratumoral; i.v., intravenous, mAbs, Monoclonal Antibodies; mIHC, Multiplex Fluorescence Immunohistochemistry; MHC, Major Histocompatibility Complex; NK, Natural Killer; NKG2D, Natural-Killer group 2 member D; NSG, NOD/SCID common γ chain knockout; PARP, Poly ADP-ribose polymerase; PBMCs, Peripheral Blood Mononuclear Cells; PBS, Phosphate-buffered saline; PDX, Patient-derived xenograft; PR, Progesterone; rhIFN-γ, Recombinant Human Interferon-γ; RPMI, Roswell Park Memorial Institute; STR, Short tandem Repeat; TCR, T Cell Receptor; TNBC, Triple Negative Breast Cancer; TSA, Tyramide Signal Amplificationhttp://dx.doi.org/10.1080/2162402X.2020.1777046cytokine-induced killer cells (cik)adoptive cells therapy (act)triple negative breast cancer (tnbc)tnbc mouse modelscetuximab |
| spellingShingle | Roberta Sommaggio Elisa Cappuzzello Anna Dalla Pietà Anna Tosi Pierangela Palmerini Debora Carpanese Lorenzo Nicolè Antonio Rosato Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells OncoImmunology cytokine-induced killer cells (cik) adoptive cells therapy (act) triple negative breast cancer (tnbc) tnbc mouse models cetuximab |
| title | Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells |
| title_full | Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells |
| title_fullStr | Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells |
| title_full_unstemmed | Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells |
| title_short | Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells |
| title_sort | adoptive cell therapy of triple negative breast cancer with redirected cytokine induced killer cells |
| topic | cytokine-induced killer cells (cik) adoptive cells therapy (act) triple negative breast cancer (tnbc) tnbc mouse models cetuximab |
| url | http://dx.doi.org/10.1080/2162402X.2020.1777046 |
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