Talaporfin Sodium

Photodynamic therapy (PDT), a local cancer treatment using photosensitizers, has been reported to enhance antitumor immune responses by inducing immunogenic cell death. Although several studies have demonstrated the synergistic antitumor effects of PDT and immune checkpoint blockage (ICB), the detailed underlying mechanisms remain poorly understood. In this study, we investigated the immunological effects of PDT with talaporfin (Tal-PDT), a clinically approved photosensitizer, using bilateral tumor-bearing mouse models. Treatment with Tal-PDT on the tumor on one side of the mouse resulted in tumor growth inhibition on the untreated opposite side. This phenomenon, accompanied by tumor antigen-specific immune reactions, is indicative of an abscopal effect. When combined with anti PD-L1 antibody, synergistic antitumor effects were observed on both the laser-treated and untreated sides. Mechanistically, Tal-PDT enhanced the induction of XCR-1+ dendritic cells in the proximal draining lymph node likely through the induction of ferroptosis in tumor cells. This, in turn, led to the systemic generation of precursor-exhausted CD8+ T cells. Moreover, talaporfin was selectively incorporated into tumor cells rather than into tumor-infiltrating T cells in vivo, leading to targeted tumor killing while preserving T cells. These beneficial effects of Tal-PDT on antitumor immunity collectively enhance ICB cancer immunotherapy. Our study demonstrates the potential of combining Tal-PDT with ICB therapy for clinical applications.

Photodynamic therapy (PDT) with talaporfin sodium shows promise as a salvage treatment for locoregional recurrence of esophageal cancer after chemoradiotherapy (CRT). However, its application in cervical esophageal cancer is limited due to anatomical challenges, such as the restricted maneuverability of standard endoscopes and difficulty in achieving stable and perpendicular laser irradiation. This study introduces a modified PDT technique using a thin endoscope with a customized attachment for lesion stabilization and precise laser targeting. The attachment, wrapped in black plastic tape, facilitated perpendicular irradiation and reduced laser scattering. Two cases of recurrent cervical esophageal cancer after CRT were successfully treated with this method. The first patient had a 10-mm, 0-IIc+IIa, cT1b lesion with severe stenosis, necessitating the use of a thin endoscope. PDT was performed with 600 J irradiation, achieving complete local control without complications, with no recurrence over four years. The second patient had a 20-mm, 0-IIa, cT1b lesion and was treated with 800 J irradiation, resulting in complete local control within three months and no recurrence at one year. Despite these promising results, this modified PDT technique has several limitations. The small sample size (two cases) limits generalizability, and long-term outcomes beyond the current follow-up period remain unknown. Additionally, the technique requires specialized equipment and expertise, potentially limiting its widespread adoption. This study presents a novel modification of PDT using transnasal thin endoscopy for precise targeting of cervical esophageal cancer lesions. This approach minimizes laser scattering and enhances procedural accuracy. We report two cases with complete local control and no recurrence over one to four years. While promising, further studies are required to assess its long-term efficacy and broader applicability.