論文 - 詳細
| RRC ID | 83586 |
|---|---|
| 著者 | Hagiyama M, Yoneshige A, Wada A, Kimura R, Ito S, Inoue T, Takeuchi F, Ito A. |
| タイトル | Efficient intracellular drug delivery by co-administration of two antibodies against cell adhesion molecule 1. |
| ジャーナル | J Control Release |
| Abstract |
Cell adhesion molecule 1 (CADM1), a single-pass transmembrane protein, is involved in oncogenesis. We previously demonstrated the therapeutic efficacy of anti-CADM1 ectodomain monoclonal antibodies against mesothelioma; however, the underlying mechanism is unclear. In the present study, we explored the molecular behavior of anti-CADM1 antibodies in CADM1-expressing tumor cells. Sequencing analyses revealed that the anti-CADM1 chicken monoclonal antibodies 3E1 and 9D2 are IgY and IgM isotype antibodies, respectively. Co-administration of 3E1 and 9D2 altered the subcellular distribution of CADM1 from the detergent-soluble fraction to the detergent-resistant fraction in tumor cells. Using recombinant chicken-mouse chimeric antibodies that had been isotype-switched from IgG to IgM, we demonstrated that the combination of the variable region of 3E1 and the constant region of IgM was required for CADM1 relocation. Cytochemical studies showed that 3E1 colocalized with late endosomes/lysosomes after co-administration with 9D2, suggesting that the CADM1-antibody complex is internalized from the cell surface to intracellular compartments by lipid-raft mediated endocytosis. Finally, 3E1 was conjugated with the antimitotic agent monomethyl auristatin E (MMAE) via a cathepsin-cleavable linker. Co-administration of 3E1-monomethyl auristatin E and 9D2 suppressed the growth of multiple types of tumor cells, and this anti-tumor activity was confirmed in a syngeneic mouse model of melanoma. 3E1 and 9D2 are promising drug delivery vehicles for CADM1-expressing tumor cells. |
| 巻・号 | 371 |
| ページ | 603-618 |
| 公開日 | 2024-7-1 |
| DOI | 10.1016/j.jconrel.2024.05.035 |
| PII | S0168-3659(24)00319-5 |
| PMID | 38782061 |
| MeSH | Animals Antibodies, Monoclonal* / administration & dosage Antibodies, Monoclonal* / immunology Cell Adhesion Molecule-1* Cell Line, Tumor Chickens Drug Delivery Systems* Female Humans Immunoglobulin M / administration & dosage Immunoglobulin M / immunology Immunoglobulins* / administration & dosage Immunoglobulins* / metabolism Melanoma, Experimental / drug therapy Melanoma, Experimental / immunology Mice Mice, Inbred C57BL Oligopeptides / administration & dosage Oligopeptides / chemistry |
| IF | 7.727 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 8 |
| 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 | B16 melanoma(RCB1283) |