Virtual Library
Start Your Search
H. Wada
Author of
-
+
P1.12 - Pulmonology/Endoscopy (ID 698)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Pulmonology/Endoscopy
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.12-002 - Nanoparticle Targeted Folate Receptor 1 Enhanced Photodynamic Therapy for Lung Cancer (ID 8471)
09:30 - 09:30 | Author(s): H. Wada
- Abstract
Background:
Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compunds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer.
Method:
The frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy.
Result:
FOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro. When irradiated with a 671 nm laser at a dose of 10 J/cm2, folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively. Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis.
Conclusion:
Folate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models.
-
+
P1.12-003 - Photothermal Ablation of Lung Cancer by Low Power Near-Infrared Laser and Topical Injection of Indocyanine Green; A Preliminary Animal Study (ID 8994)
09:30 - 09:30 | Author(s): H. Wada
- Abstract
Background:
Surgical resection by lobectomy with systematic lymph node dissection is the gold standard of treatment for early stage non-small cell lung cancer. However, minimally invasive tumor ablation can be an alternative treatment for patients not eligible for surgery due to comorbidities. The present study was designed to evaluate the efficacy of photothermal ablation therapy for lung cancer by low power near-infrared laser and topical injection of Indocyanine green (ICG).
Method:
6 New Zealand white rabbits were employed for the study. Tumor suspension containing VX2 cancer cells with growth factor reduced Matrigel was inoculated into the lung using an ultrathin bronchoscope. 3 rabbits were treated by laser ablation therapy with topical injection of ICG. Another 3 rabbits were treated by laser ablation alone. All tumors were irradiated with a laser with 500 mW output at 808 nm for 15 min. The tumors were examined histopathologically to assess the ablated areas.
Result:
Figure 1The maximum surface temperature of the tumor in rabbits treated by ICG/laser and laser alone were more than 58°C and less than 40°C, respectively. The ablated areas in the rabbits using ICG/laser were statistically larger than those in the rabbits using laser alone (ICG/laser: 0.49±0.27 cm[2] vs laser alone: 0.02±0.002 cm[2]) (p < 0.05).
Conclusion:
We clarified the efficacy of the photothermal treatment by low power near-infrared laser and topical injection of ICG using a rabbit VX2 orthotopic lung cancer model. This system may be able to be applied for transbronchial laser ablation of peripheral lung cancers.
-
+
P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P2.07-008 - Does PD-L1 Expression of the Archive Surgical Specimen of Primary Tumor Predict the Sensitivity of Recurrence to Nivolumab in Patients with NSCLC? (ID 8041)
09:30 - 09:30 | Author(s): H. Wada
- Abstract
Background:
Nivolumab is an immune checkpoint inhibitor targeting human IgG4 programmed death 1 for advanced or recurrent non-small lung cancer (NSCLC), and programmed death ligand 1 (PD-L1) expression of tumor tissue is expected to be a biomarker of the sensitivity to Nivolumab. More recent biopsy is likely to be more suitable since PD-L1 expression of tumor cells is influenced by time or by anti-tumor therapies such as chemotherapy or radiotherapy, and most clinical studies have referred to the PD-L1 expression using the latest biopsy samples before administration of Nivolumab. Therefore, it remains controversial whether PD-L1 expression of the archive specimen obtained at the time of initial surgery for primary disease is correlated with the sensitivity of recurrent diseases to Nivolumab.
Method:
We retrospectively reviewed 10 NSCLC patients who had undergone radical surgery for primary tumor and received Nivolumab for their recurrent diseases. The median interval between the initial surgery and Nivolumab administration was 28.1 months (2-75), and median number of anti-tumor regimens prior to Nivolumab was 2.2 (1-5). Archive specimens of primary tumors and second biopsy samples of recurrent diseases from the 10 patients were stained to measure PD-L1 expression both with the PD-L1 IHC 28-8 pharmDx Daco (assay 28-8), and with the PD-L1 IHC 22C3 pharmDx Daco (assay 22C3).
Result:
Among the 10 patients, complete response (CR)/partial response (PR)/ stable disease (SD)/progressive disease (PD) for Nivolumab were 1/2/3/4 patients, respectively. All patients had PD-L1 expressions as tumor proportion score (TPS)≧1%, of which 7 showed TPS≧10% in the assay 28-8. All 3 patients (30%) with CR/PR showed TPS≧10%. The TPS obtained by assays 28-8 and 22C3 were similar in 9 of 10 patients. Two patients underwent biopsies for their recurrent sites, which showed decreased PD-L1 expression compared with primary tumor, resulted in PD for Nivolumab.
Conclusion:
The PD-L1 expressions of surgical archive specimen might be almost associated with the sensitivity to Nivolumab, however, time and antitumor therapies may modulate the PD-L1 expressions and might be able to affect the sensitivity to Nivolumab. Further pre-clinical and clinical studies are warranted to evaluate the availability of surgical archive specimen in the treatment of postoperative recurrence by the immunocheckpoint inhibition.
