• First study showing that post‑photoimmunotherapy PGE₂ production driven by COX‑2 activity may contribute to edema formation
• Findings suggest that prophylactic COX‑2 inhibition may mitigate edema and improve treatment safety

SAN DIEGO — April 21, 2026 — Rakuten Medical, Inc., a global biotechnology company developing and commercializing the Alluminox® platform-based photoimmunotherapy, announces a poster titled “COX-2/PGE2 driven, photoimmunotherapy-induced edema is reduced by prophylactic NSAIDs in mouse tumor models” was presented today at the 2026 Annual Meeting of the American Association for Cancer Research (AACR 2026) in San Diego. The poster examined the mechanism underlying photoimmunotherapy-induced edema and the potential of cyclooxygenase‑2 (COX‑2) inhibition to reduce edema.

COX‑2 is an inducible enzyme that is upregulated under inflammatory conditions. Previous mouse studies by Rakuten Medical showed that prophylactic selective COX‑2 inhibition reduced the volume of photoimmunotherapy-induced edema by 30–50%.

In this AACR poster presentation, induction of COX‑2 expression and secretion of prostaglandin E₂ (PGE₂) were observed following photoimmunotherapy. While co‑incubation with either a selective COX‑2 inhibitor or a pan‑COX inhibitor did not suppress COX‑2 expression, PGE₂ secretion was blocked by these agents. PGE₂ is known to be produced predominantly via COX‑2 activity under inflammatory conditions and to contribute to edema formation by increasing vascular permeability. Importantly, in the mouse tumor models evaluated here, COX inhibition did not affect anti-tumor efficacy.

Collectively, these results suggest that photoimmunotherapy‑induced edema is mediated by induction of COX‑2 expression followed by COX‑2 activity-dependent PGE₂ production; also, prophylactic COX‑2 inhibition may allow better management of edema.

Photoimmunotherapy based on Rakuten Medical’s proprietary Alluminox platform involves the administration of a drug that selectively binds to target cells, followed by laser illumination that has been shown in the preclinical setting to rapidly and selectively disrupt the cell membrane of the targeted cells. From early clinical studies¹ and from real-world clinical use in Japan² in head and neck cancer, photoimmunotherapy with ASP-1929 suggests that the safety profile may be manageable: of note, edema is a commonly reported adverse event, and in cases where tongue swelling or laryngeal edema poses a risk of airway obstruction, prophylactic interventions such as tracheostomy may be required. These measures can place a significant burden on patients, underscoring the need for less invasive approaches to edema management.

Disclaimer: Rakuten Medical’s photoimmunotherapy is investigational outside Japan.

Strategies to manage photoimmunotherapy‑induced edema are being evaluated in real‑world settings through a multicenter investigator‑initiated study in Japan. Based on the findings of this preclinical study and ongoing clinical research, Rakuten Medical continues to evaluate safety, with aims to optimize the safety of its Alluminox platform and better manage patient burden.

Key findings presented at AACR 2026

Title: COX-2/PGE₂ driven, photoimmunotherapy-induced edema is reduced by prophylactic NSAIDs in mouse tumor models

Poster Link: View/Download Poster [PDF]

Abstract Number: 4297

Abstract Link: https://www.abstractsonline.com/pp8/#!/21436/presentation/5131

• In vitro, Ephrin A2 (EphA2)-expressing CT26 and LL2 tumor models were incubated with an anti‑EphA2-IR700 conjugate ± light, and COX‑2 expression was assessed by real‑time PCR and Western blot, showing increased expression following photoimmunotherapy light illumination.
• Co‑incubation with the selective COX‑2 inhibitor robenacoxib or the pan‑COX inhibitor flurbiprofen did not suppress post‑photoimmunotherapy COX‑2 expression.
• ELISA analysis revealed immediate post‑photoimmunotherapy induction of PGE₂ secretion, which was completely blocked by COX inhibition.
• In vivo, photoimmunotherapy‑induced edema peaked six hours post‑photoimmunotherapy in CT26‑EphA2 and LL2‑EphA2 mouse tumor models.
• Prophylactic treatment with either COX inhibitor significantly reduced edema (p ≤0001).
• COX‑2 expression was increased post‑photoimmunotherapy in tumor lysates, while COX‑1 expression was unchanged and unaffected by COX inhibition.
• Elevated circulating PGE₂ metabolites post‑photoimmunotherapy were observed in vivo and were abrogated by COX inhibition.
• In a human hypopharyngeal cancer xenograft model, edema similarly peaked at six hours post‑photoimmunotherapy and was significantly reduced by prophylactic COX inhibition (p ≤0001).
• No compromise in photoimmunotherapy-induced antitumor efficacy was observed with COX inhibitor treatment.

 

1. Cognetti DM, Johnson JM, Curry JM, et al. Phase 1/2a, open‑label, multicenter study of RM‑1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma. Head Neck. 2021;43(12):3875–3887. doi:10.1002/hed.26885
2. Shinozaki T, et al. Real‑world clinical experience with ASP‑1929 photoimmunotherapy in head and neck cancer. 34th Annual Meeting of the Japanese Society for Head and Neck Surgery; January 2025.