Near-Infrared Photoimmunotherapy Targeting Podoplanin-Expressing Cancer Cells and Cancer-Associated Fibroblasts

Abstract

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.

Phototruncation cell tracking with near-infrared photoimmunotherapy using heptamethine cyanine dye to visualise migratory dynamics of immune cells

“…Our previous studies reported no significant increase in intratumoural Treg populations after NIR-PIT. 25 , 39 Thus, we further assessed the migration of immunosuppressive cells including Tregs and MDSCs from the TDLN to the tumour three days after hEGFR-targeted NIR-PIT using mEERL-hEGFR tumour models. Twenty-four hours after 780 nm light irradiation, the percentage of Cy5-labeled Tregs and MDSCs was comparable between the NIR-PIT and No NIR-PIT groups ( Fig.…”

Tumor Suppression by Anti-Fibroblast Activation Protein Near-Infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts

“…It has been reported that higher PDPN expression is associated with poorer outcomes in human colorectal carcinomas [59] and is considered to be another promising method of targeting CAFs [60]. Aside from high expression on CAFs, PDPN is also highly expressed in lymphatic endothelium, both in normal tissues and during tumorigenesis.…”

Cancer‐Associated Fibroblast‐Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer

“…Recently, various therapeutic approaches targeting cancer‐associated fibroblasts (CAFs), including the use of specific antibodies and antibody conjugates with photosensitizers, have been documented. [ 70 , 71 ] BC exhibits a high affinity for endoscopic therapeutic modalities, and targeting CAFs in situ may yield a more effective outcome in inhibiting tumor recurrence. These findings shed light on the regulatory mechanisms involved in recurrent BC and inform the development of new therapeutic strategies.…”