論文 - 詳細
| RRC ID | 68100 |
|---|---|
| 著者 | Panaampon J, Kariya R, Okada S. |
| タイトル | Efficacy and mechanism of the anti-CD38 monoclonal antibody Daratumumab against primary effusion lymphoma. |
| ジャーナル | Cancer Immunol Immunother |
| Abstract |
Primary effusion lymphoma (PEL) is a rare, aggressive B cell non-Hodgkin's lymphoma of the body cavities with malignant effusions. The prognosis is poor, and no optimal treatment has been established. CD38 is a type II transmembrane glycoprotein known to overexpress in multiple myeloma (MM). Daratumumab (DARA), a human CD38-targeting monoclonal antibody (mAb), is approved for MM treatment. In this study, we found expression of CD38 on PEL cells and assessed the anti-PEL activity of DARA. We found that both KHYG-1 and N6 (CD16-transfected KHYG-1) NK cell lines showed direct killing activity against PEL cells with induction of CD107a, and NK-mediated cytotoxicity by N6NK (CD16+) cells increased with DARA treatment. We confirmed direct NK activity and antibody-dependent cell cytotoxicity (ADCC) by expanded NK cells, indicating that DARA has high ADCC activity. We elucidated the antibody-dependent cell phagocytosis (ADCP) by using human monocyte-derived macrophages (MDMs) and mouse peritoneal macrophages. DARA also showed potent complement-dependent cytolysis (CDC) toward PEL. DARA also induced PEL cell death in the presence of a cross-linking antibody. Moreover, treatment with DARA inhibited tumor growth in a PEL xenograft mouse model. These results provide preclinical evidence that Ab targeting of CD38 could be an effective therapeutic strategy for the treatment of PEL. |
| 巻・号 | 71(5) |
| ページ | 1017-1031 |
| 公開日 | 2022-5-1 |
| DOI | 10.1007/s00262-021-03054-8 |
| PII | 10.1007/s00262-021-03054-8 |
| PMID | 34545416 |
| PMC | PMC10991639 |
| MeSH | ADP-ribosyl Cyclase 1 Animals Antibodies, Monoclonal / pharmacology Antibodies, Monoclonal / therapeutic use Antibody-Dependent Cell Cytotoxicity Antineoplastic Agents* / therapeutic use Humans Lymphoma, Primary Effusion* / drug therapy Mice Multiple Myeloma* |
| IF | 5.442 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | K562 |