Et-6 efficacy of near-infrared photoimmunotherapy targeting podoplanin in malignant gliomas

Abstract Background Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment based on a conjugate of photosensitizer IR700 and an antibody which selectively binds to the surface antigen of cancer cells. Upon exposure to near infrared light, which does not harm normal tissues, cancer cells are selectively killed. Clinical application for EGFR amplified head and neck cancer has already been realized but is still in the preclinical stages of research for brain tumors. Finding a surface antigen which is selective to cancer cells is key to the effective application of NIR-PIT. In IDH-wildtype gliomas, we found that podoplanin (PDPN) is a promising candidate. PDPN is a transmembrane sialoglycoprotein highly expressed in IDH-wildtype gliomas and other cancers. Methods Three PDPN-positive (NGT-11, NGT-41, LN319) and three PDPN-negative (T98G, U87MG, U251MG) glioblastoma cell lines were treated with PDPN-IR700 conjugate and exposed to near infrared light. Cytotoxicity was assessed by cell viability assays. Next, we treated subcutaneous mouse xenografts by NIR-PIT. Results Cytotoxicity was only observed after NIR-PIT using PDPN-conjugate in cell lines expressing PDPN. This cytotoxicity was dose-dependent to near infrared light exposure, and most pronounced in LN319 cell line, which expressed the highest levels of PDPN. Time lapse videos revealed instantaneous expanding, followed by rounding of dead cells after treatment. NIR-PIT treated subcutaneous xenografts showed significantly smaller tumor sizes compared to control, and pathological investigation revealed selective and extensive necrosis of tumor tissue. Discussion/conclusion PDPN is highly expressed in IDH-wildtype gliomas, and we found that NIR-PIT was highly effective in treating PDPN expressing glioblastoma cell lines. NIR-PIT is anticipated to be more selective and cytotoxic than photodynamic therapy and is a promising new treatment strategy for IDH-wildtype gliomas.