論文 - 詳細
| RRC ID | 71922 |
|---|---|
| 著者 | Badiee P, Maritz MF, Dmochowska N, Cheah E, Thierry B. |
| タイトル | Intratumoral Anti-PD-1 Nanoformulation Improves Its Biodistribution. |
| ジャーナル | ACS Appl Mater Interfaces |
| Abstract |
Intratumoral administration of immune checkpoint inhibitors, such as programmed cell death-1 antibodies (aPD-1), is a promising approach toward addressing both the low patients' responses and high off-target toxicity, but good preclinical results have not translated in phase I clinical studies as significant off-target toxicities were observed. We hypothesized that the nanoformulation of aPD-1 could alter both their loco-regional and systemic distribution following intratumoral administration. To test this hypothesis, we developed an aPD-1 nanoformulation (aPD-1 NPs) and investigated its biodistribution following intratumoral injection in an orthotopic mice model of head and neck cancer. Biodistribution analysis demonstrated a significantly lower distribution in off-target organs of the nanoformulated aPD-1 compared to free antibodies. On the other hand, both aPD-1 NPs and free aPD-1 yielded a significantly higher tumor and tumor draining lymph node accumulation than the systemically administrated free aPD-1 used as the current clinical benchmark. In a set of comprehensive in vitro biological studies, aPD-1 NPs effectively inhibited PD-1 expression on T-cells to a similar extent to free aPD-1 and efficiently potentiated the cytotoxicity of T-cells against head and neck cancer cells in vitro. Further studies are warranted to assess the potential of this intratumoral administration of aPD-1 nanoformulation in alleviating the toxicity and enhancing the tumor efficacy of immune checkpoint inhibitors. |
| 巻・号 | 14(14) |
| ページ | 15881-15893 |
| 公開日 | 2022-4-13 |
| DOI | 10.1021/acsami.1c22479 |
| PMID | 35357803 |
| MeSH | Animals Antibodies Head and Neck Neoplasms* / drug therapy Humans Immune Checkpoint Inhibitors* Immunotherapy / methods Mice T-Lymphocytes Tissue Distribution |
| IF | 8.758 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 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 | |
| 遺伝子材料 | CSII-EF-mRFP1 (RDB06387) mVenus-hGeminin(1/110) / pCSII-EF (RDB15271) mCherry-hCdt1(30/120)/ pCSII-EF (RDB15273) |