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
|
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) |