RRC ID 71922
Author Badiee P, Maritz MF, Dmochowska N, Cheah E, Thierry B.
Title Intratumoral Anti-PD-1 Nanoformulation Improves Its Biodistribution.
Journal 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.
Volume 14(14)
Pages 15881-15893
Published 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
DNA material CSII-EF-mRFP1 (RDB06387) mVenus-hGeminin(1/110) / pCSII-EF (RDB15271) mCherry-hCdt1(30/120)/ pCSII-EF (RDB15273)