Immune Checkpoint Blockade Mediated by a Small-Molecule Nanoinhibitor Targeting the PD-1/PD-L1 Pathway Synergizes with Photodynamic Therapy to Elicit Antitumor Immunity and Antimetastatic Effects on Breast Cancer

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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Author(s)

  • Zhiyan Zhu
  • Hongying Lv
  • Futian Li
  • Shuqing Sun
  • Juan Li

Related Research Unit(s)

Detail(s)

Original languageEnglish
Article number1903881
Journal / PublicationSmall
Volume15
Issue number49
Online published8 Nov 2019
Publication statusPublished - 6 Dec 2019

Abstract

Targeting programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immunologic checkpoint blockade with monoclonal antibodies has achieved recent clinical success in antitumor therapy. However, therapeutic antibodies exhibit several issues such as limited tumor penetration, immunogenicity, and costly production. Here, Bristol-Myers Squibb nanoparticles (NPs) are prepared using a reprecipitation method. The NPs have advantages including passive targeting, hydrophilic and nontoxic features, and a 100% drug loading rate. BMS-202 is a small-molecule inhibitor of the PD-1/PD-L1 interaction that is developed by BMS. Transfer of BMS-202 NPs to 4T1 tumor-bearing mice results in markedly slower tumor growth to the same degree as treatment with anti-PD-L1 monoclonal antibody (α-PD-L1). Consistently, the combination of Ce6 NPs with BMS-202 NPs or α-PD-L1 in parallel shows more efficacious antitumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of antigen-specific T cells into the tumors. Thus, inhibition rates of primary and distant tumors reach >90%. In addition, BMS-202 NPs are able to attack spreading metastatic lung tumors and offer immune-memory protection to prevent tumor relapse. These results indicate that BMS-202 NPs possess effects similar to α-PD-L1 in the therapies of 4T1 tumors. Therefore, this work reveals the possibility of replacing the antibody used in immunotherapy for tumors with BMS-202 NPs.

Research Area(s)

  • breast tumors, immune checkpoint blockade, PD-1, PD-L1, photodynamic therapy, small molecular inhibitors, IMMUNOGENIC CELL-DEATH, DRUG-DELIVERY, NANOPARTICLES, IMMUNOTHERAPY, MEMORY, COMBINATION, METASTASIS, INHIBITORS, SIGNALS, TUMORS

Citation Format(s)

Immune Checkpoint Blockade Mediated by a Small-Molecule Nanoinhibitor Targeting the PD-1/PD-L1 Pathway Synergizes with Photodynamic Therapy to Elicit Antitumor Immunity and Antimetastatic Effects on Breast Cancer. / Zhang, Rui; Zhu, Zhiyan; Lv, Hongying; Li, Futian; Sun, Shuqing; Li, Juan; Lee, Chun-Sing.

In: Small, Vol. 15, No. 49, 1903881, 06.12.2019.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review