Utilizing molecular resonance-localized surface plasmon resonance coupling for copper ion detection in plasma.

The rapid, point-of-care detection of copper in plasma can greatly aid in a large number of diseases where copper has been implicated to be an important factor, such as cancer, Alzheimer's and Diabetes mellitus. Localized surface plasmon resonance (LSPR) technologies show promise in the inexpensive detection of copper, whereas previous platforms are plagued with selectivity and sensitivity issues. Herein, we have created a sensitive and selective on-chip copper sensor which can produce a colorimetric reading in 60 minutes. The selectivity of the assay is based on 'Click' chemistry and is shown to have little interference with other metal ions present in plasma. The sensitivity of the assay is generated from the coupling of the molecular resonance of a dye and the LSPR of the gold nanoparticles. The assay is capable of measuring copper concentrations in human plasma as low as 4 µM and the linear range of sensitivity, 4 to 20 µM, is in the physiologically relevant range. This robust, colorimetric assay should prove useful in a point-of-care setting.

Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial.

PURPOSE: The efficacy of cetuximab is poor in metastatic head and neck squamous cell carcinoma (HNSCC). Cetuximab initiates natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity, with resultant recruitment of immune cells and suppression of antitumor immunity. We hypothesized that adding an immune-checkpoint inhibitor (ICI) could overcome this and lead to an enhanced antitumor response. PATIENTS AND METHODS: A phase II study of cetuximab and durvalumab in metastatic HNSCC was conducted. Eligible patients had measurable disease. Patients who had received both cetuximab and an ICI were excluded. The primary endpoint was objective response rate (ORR) by RECIST 1.1 at 6 months. RESULTS: As of April 2022, 35 patients enrolled, of whom 33 received at least 1 dose of durvalumab and were included in the response analysis. Eleven patients (33%) had received prior platinum-based chemotherapy, 10 an ICI (30%), and 1 patient (3%) cetuximab. ORR was 39% (13/33) with a median duration of response of 8.6 months [95% confidence interval (CI): 6.5-16.8]. Median progression-free and overall survivals were 5.8 months (95% CI: 3.7-14.1) and 9.6 months (95% CI: 4.8-16.3), respectively. There were 16 grade 3 treatment-related adverse events (TRAE) and one grade 4 TRAE, with no treatment-related deaths. Overall and progression-free survival did not correlate with PD-L1 status. NK cell cytotoxic activity was increased by cetuximab and further increased with the addition of durvalumab in responders. CONCLUSIONS: The combination of cetuximab and durvalumab demonstrated durable activity with a tolerable safety profile in metastatic HNSCC and warrants further investigation.