Interleukin 15 (IL15)-based near-infrared photoimmunotherapy.

Area of Science:

• Oncology
• Immunotherapy
• Photodynamic Therapy

Background:

• Near-infrared photoimmunotherapy (NIR-PIT) utilizes targeted conjugates activated by near-infrared light for selective cancer cell destruction.
• Traditional NIR-PIT relies on monoclonal antibodies for targeting, but alternative moieties offer new therapeutic avenues.

Purpose of the Study:

• To investigate the efficacy of NIR-PIT using interleukin-15 (IL15) conjugated to the photoabsorber IRDye700DX (IR700).
• To evaluate the therapeutic potential of cytokine-based NIR-PIT in a solid cancer model.

Main Methods:

• Conjugation of IL15 with IR700 to create IL15-IR700 for targeted delivery.
• In vitro assessment of IL15-IR700 binding, cytotoxicity, and morphological changes upon NIR light activation.
• In vivo evaluation of IL15-IR700 retention, tumor growth suppression, and immune response following intratumoral or intravenous injection.

Main Results:

• IL15-IR700 effectively bound to MC38 HIL15Rα cells, inducing significant cytotoxicity and morphological changes.
• Intratumoral injection of IL15-IR700 demonstrated prolonged tumor retention and superior tumor growth suppression compared to intravenous administration.
• NIR-PIT with IL15-IR700 stimulated a host immune response and induced necrosis-like changes in tumor tissue.

Conclusions:

• Cytokine-based NIR-PIT using IL15-IR700 is a viable therapeutic strategy for solid cancers.
• IL15-IR700 offers a novel approach to enhance the selectivity and efficacy of NIR-PIT.
• This study highlights the potential of leveraging cytokines in photoimmunotherapy for improved cancer treatment outcomes.