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Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines
DC Field | Value | Language |
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dc.contributor.author | Park, Ji-Eun | - |
dc.contributor.author | Kim, Seong-Eun | - |
dc.contributor.author | Keam, Bhumsuk | - |
dc.contributor.author | Park, Ha-Ram | - |
dc.contributor.author | Kim, Soyeon | - |
dc.contributor.author | Kim, Miso | - |
dc.contributor.author | Kim, Tae Min | - |
dc.contributor.author | Doh, Junsang | - |
dc.contributor.author | Kim, Dong-Wan | - |
dc.contributor.author | Heo, Dae Seog | - |
dc.date.accessioned | 2021-01-31T08:06:47Z | - |
dc.date.available | 2021-01-31T08:06:47Z | - |
dc.date.created | 2020-10-19 | - |
dc.date.created | 2020-10-19 | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Journal for ImmunoTherapy of Cancer, Vol.8 No.2, p. e000873 | - |
dc.identifier.issn | 2051-1426 | - |
dc.identifier.other | 113243 | - |
dc.identifier.uri | https://hdl.handle.net/10371/171814 | - |
dc.description.abstract | Background Although programmed cell death-1/programmed death-ligand 1 (PD-L1) inhibitors show remarkable antitumor activity, a large portion of patients with cancer, even those with high PD-L1-expressing tumors, do not respond to their effects. Most PD-L1 inhibitors contain modified fragment crystallizable region (Fc) receptor binding sites to prevent antibody-dependent cellular cytotoxicity (ADCC) against PD-L1-expressing non-tumor cells. However, natural killer (NK) cells have specific antitumor activity in the presence of tumor-targeting antibody through ADCC, which could enhance NK cell-induced cytotoxicity. We evaluated the antitumor efficacy of ADCC via anti-PD-L1 monoclonal antibodies (mAbs) and NK cells against several PD-L1-positive cancer cell lines. Methods Various cancer cell lines were used as target cell lines. Surface PD-L1 expression was analyzed by flow cytometry. IMC-001 and anti-hPD-L1-hIgG1 were tested as anti-PD-L1 mAbs with ADCC and atezolizumab as an anti-PD-L1 mAb without ADCC. NK cell cytotoxicity was measured by(51)Cr-release assay and CD107a degranulation assay. Also, live cell imaging was performed to evaluate cytotoxicity in a single-cell level. NK-92-CD16 (CD16-transduced NK-92 cell line) and peripheral blood mononuclear cells from healthy donors, respectively, were used as an effector cell. Fc gamma RIIIa (CD16a)-V158F genotyping was performed for healthy donors. Results We demonstrated that the cytotoxicity of NK-92-CD16 cells toward PD-L1-positive cancer cell lines was significantly enhanced in the presence of anti-PD-L1 mAb with ADCC. We also noted a significant increase in primary human NK cell cytotoxicity against PD-L1-positive human cancer cells when cocultured with anti-PD-L1 mAb with ADCC. Moreover, NK cells expressing aFCGR3Ahigh-affinity genotype displayed higher anti-PD-L1 mAb-mediated ADCC lysis of tumor cells than donors with a low-affinity genotype. Conclusion These results suggest that NK cells induce an ADCC response in combination with anti-PD-L1 mAbs, which helps promote ADCC antitumor activity against PD-L1-positive tumors. This study provides support for NK cell immunotherapy against high PD-L1-expressing tumors in combination with ADCC through anti-PD-L1 mAbs. | - |
dc.language | 영어 | - |
dc.publisher | BioMed Central | - |
dc.title | Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 도준상 | - |
dc.contributor.AlternativeAuthor | 김동완 | - |
dc.contributor.AlternativeAuthor | 허대석 | - |
dc.identifier.doi | 10.1136/jitc-2020-000873 | - |
dc.citation.journaltitle | Journal for ImmunoTherapy of Cancer | - |
dc.identifier.wosid | 000573896000003 | - |
dc.identifier.scopusid | 2-s2.0-85089794266 | - |
dc.citation.number | 2 | - |
dc.citation.startpage | e000873 | - |
dc.citation.volume | 8 | - |
dc.identifier.sci | 000573896000003 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Doh, Junsang | - |
dc.contributor.affiliatedAuthor | Kim, Dong-Wan | - |
dc.contributor.affiliatedAuthor | Heo, Dae Seog | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ACQUIRED-RESISTANCE | - |
dc.subject.keywordPlus | TUMOR-CELLS | - |
dc.subject.keywordPlus | POLYMORPHISMS | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | MPDL3280A | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | CD107A | - |
dc.subject.keywordPlus | PD-L1 | - |
dc.subject.keywordAuthor | killer cells | - |
dc.subject.keywordAuthor | natural | - |
dc.subject.keywordAuthor | immunotherapy | - |
dc.subject.keywordAuthor | cytotoxicity | - |
dc.subject.keywordAuthor | immunological | - |
dc.subject.keywordAuthor | lung neoplasms | - |
dc.subject.keywordAuthor | head and neck neoplasms | - |
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