Nanoparticulated Anti-Programmed Cell Death-1 Antibody Improves Localized Immune Checkpoint Blockade Therapy

TL;DR

Researchers developed a nanoparticle-based antibody treatment that improves localized cancer therapy by boosting immune response and reducing side effects.

Contribution

A novel nanoformulation of anti-PD-1 antibody using mesoporous polydopamine nanoparticles enhances immune checkpoint blockade therapy.

Findings

The nanoformulation increased antagonistic activity of aPD-1 against PD-1 receptors, blocking immune checkpoint signaling.

Local intratumoral injection of the nanoformulation enhanced tumor retention and antitumor efficacy.

Nano-ICI treatment effectively orchestrated antitumor immunity for both local and systemic cancer treatment.

Abstract

Immune checkpoint inhibitors (ICIs) have successfully transformed clinical oncology against various cancers. However, their widespread utility is limited by low response rates and severe adverse events; thus, a safe and effective approach is required to address these issues. Here, we report the nanoengineering of an anti-programmed cell death-1 antibody (aPD-1) to boost the therapeutic effects following direct local administration into tumors. Specifically, we prepared an aPD-1 nanoformulation using biocompatible mesoporous polydopamine nanoparticles (MPNs) that allow facile and efficient surface functionalization of aPD-1 via latent reactivity to proteins. The nanoformulation increased the antagonistic activity of aPD-1 against PD-1 receptors by enhancing their avidity interactions, effectively blocking PD-1 immune checkpoint signaling in T cells to restore their activation and effector function. The nanoformulation administered via local intratumoral injection enhanced tumor retention of aPD-1 and elicited strong antitumor efficacy against local tumors and long-term tumor recurrence. Our results indicate that robust immune checkpoint signaling blockade in the local tumors using nano-ICI treatment can effectively orchestrate antitumor immunity for local and systemic cancer treatment. Overall, this study underscores the potential of a biomaterial-based nanoengineering approach for improving the efficacy and safety of antibody-based ICI therapy with localized tumor treatment.

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