Prophylactic administration of a selective COX-2 inhibitor reduces the volume of edema associated with photoimmunotherapy by 30-50%
Reduced edema volume by 25%, even when administered post photoimmunotherapy
Suggested the COX-2 inhibitor may manage edema without compromising anti-tumor efficacy
SAN DIEGO, April 11, 2024 /PRNewswire/ — Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, today announced a poster presentation of its study to manage edema following photoimmunotherapy at the 115th Annual Meeting of the American Association for Cancer Research (AACR 2024) in San Diego, California, on April 8th, 2024.
In the study presented in this poster, Rakuten Medical developed a mouse tumor model to assess edema following photoimmunotherapy and evaluated various steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) for edema reduction using the model. As a result, a reduction in edema was observed when the selective COX-2 inhibitor meloxicam, one of NSAIDs, was administered before or after illumination of photoimmunotherapy (30-50% reduction with prophylactic administration, 25% reduction with post-illumination administration). It was also confirmed that the reduction in edema with meloxicam was not associated with a loss of therapeutic benefit based on measurement of tumor growth.
Rakuten Medical’s photoimmunotherapy consists of a drug and a laser light. In pre-clinical studies, local illumination results in highly selective and rapid necrosis of target cells such as tumors. Early clinical studies have shown a manageable safety profile for head and neck cancer.* However, edema is a commonly reported adverse event with severe laryngeal edema noted in some patients, and prophylactic tracheostomy is required if laryngeal edema threatens to obstruct the airway. Thus, new tools to manage edema are needed to reduce the burden on the patient. Based on the results of this study, Rakuten Medical will conduct further research to address the challenges of edema associated with photoimmunotherapy in clinical trials and in clinical practice.
Key findings presented at AACR 2024Title: Reduction in photoimmunotherapy-induced edema with COX-2 inhibition: Combatting clinically relevant adverse events without compromising efficacyAbstract Number: 1415
Abstract Link: https://www.abstractsonline.com/pp8/#!/20272/presentation/5855
Cohorts of mice bearing syngeneic LL/2 tumors engineered to express Ephrin A2 (EphA2) were administered an anti-EphA2 antibody conjugated to IR700 (conjugate) or saline control and illuminated with light. Control mice did not generate edema, but mice treated with conjugate plus light showed a light-dose dependent increase in edema volume which peaked at 6h post light delivery.
Inflammatory cytokine and immune cell populations in the blood and tumor region were then evaluated at the onset (2h post-light), peak (6h), and resolution (24h) of the edema associated with photoimmunotherapy. The results showed a striking increase in neutrophils in the blood at the peak of edema formation (500-fold greater than control mice, n=10, p