Intratumoral anti-PD-1 nanoformulation improves its biodistribution
Date
2022
Authors
Badiee, P.
Maritz, M.F.
Dmochowska, N.
Cheah, E.
Thierry, B.
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Journal article
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ACS applied materials & interfaces, 2022; 14(14):15881-15893
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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.
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Data source: Supporting information, https://doi.org/10.1021/acsami.1c22479
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Copyright 2022 American Chemical Society