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P.L. Choyke
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-032 - Near Infrared Photoimmunotherapy for Pleural Metastases: Preclinical Experience (ID 1022)
09:30 - 09:30 | Author(s): P.L. Choyke
- Abstract
Background:
Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet they are difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a new cancer treatment that utilizes the specificity of intravenously injected antibodies to target photosensitizers to specific cancers (Figure). Since one interesting property of the lung is that it transmits light better than any other organ, light therapy is a viable alternative therapy. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated pleural metastases in a non-small cell lung cancer (NSCLC) model.
Methods:
In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted within the intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. Body weight was measured as an index of systemic toxicity.
Results:
In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led to significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to a significant reduction in the volume of pleural metastases 1 day after PIT (p = 0.0180)(Figure). Fluorescence thoracoscopy confirmed this result (Figure). Body weight ratio showed no significant reduction in NIR-PIT treated mice. Figure 1
Conclusion:
NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC. We foresee NIR-PIT as an adjuvant to surgery with an initial conventional debulking procedure followed by NIR-PIT to “mop up” residual disease. Moreover, it would be feasible to deliver light via thoracoscopy, bronchoscopy or even during open-surgery. Thus, although this particular animal model is not typical of NSCLC, the feasibility of treating thoracic malignancies with light therapy is demonstrated. NIR-PIT is a promising therapy for disseminated pleural tumors.
