Near-Infrared Photoimmunotherapy Targeting Podoplanin-Expressing Cancer Cells and Cancer-Associated Fibroblasts.
Takuya KatoAki FurusawaRyuhei OkadaFuyuki F InagakiHiroaki WakiyamaHideyuki FurumotoHiroshi FukushimaShuhei OkuyamaPeter C BlackHisataka KobayashiPublished in: Molecular cancer therapeutics (2022)
Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that utilizes an antibody-IRDye700DX (IR700) conjugate that binds to a target followed by the application of NIR light that results in dramatic changes in solubility of the conjugate leading to rapid cell membrane damage and highly immunogenic cell death. NIR-PIT has been used clinically in treating advanced head and neck cancers using an anti-epidermal growth factor receptor (EGFR) antibody-IR700 conjugate and has been conditionally approved for clinical use in Japan. NIR-PIT can be employed using a wide range of targeting antibodies. Podoplanin (PDPN), also known as gp38, is a 38 kDa type-1 transmembrane associated with lymphatic vessels. In cancer cells and cancer-associated fibroblasts (CAFs), PDPN expression has been widely reported and correlates with poor outcomes in several cancer types. In this study, we evaluated the efficacy of PDPN-targeted NIR-PIT in a syngenetic mouse model of cancer. PDPN-targeted NIR-PIT destroyed PDPN-expressing cancer cells and CAFs selectively, suppressing tumor progression and prolonging survival with minimal damage to lymphatic vessels compared with the control group. Interestingly, PDPN-targeted NIR-PIT also exerted a therapeutic effect by targeting CAFs in tumor models which do not express PDPN. Furthermore, increased cytotoxic T cells in the tumor bed after PDPN-targeted NIR-PIT were observed, suggesting enhanced host antitumor immunity. Thus, PDPN-targeted NIR-PIT is a promising new cancer therapy strategy for PDPN-expressing cancer cells and CAFs.
Keyphrases
- cancer therapy
- drug release
- drug delivery
- photodynamic therapy
- fluorescence imaging
- fluorescent probe
- epidermal growth factor receptor
- cell death
- mouse model
- tyrosine kinase
- oxidative stress
- signaling pathway
- metabolic syndrome
- young adults
- long non coding rna
- advanced non small cell lung cancer
- childhood cancer
- anti inflammatory