LAUSR

Introduction: Antibody therapy has been successfully used for several caners, but the efficacy is still limited. To select patients that respond well to the therapy, development of companion diagnostics is essential. Although PD-L1 expression determined by immunohistochemistry has been shown to be a marker to select patients with non-small-cell lung cancer who will benefit from antibody therapy, its potential for Nivolumab treatment in renal cell carcinoma (RCC) patients is unclear. Detection of the soluble form of PD-1 in serum has been reported, but there are few studies demonstrating its clinical role in RCC. Antibody-based assays may rely on characteristics and quality of antibody used. We hypothesized that the use of Nivolumab as a capture antibody in ELISA would give more clinically relevant results to evaluate the serum PD-1 levels in RCC patients. Materials and Methods: After approval of the study by the Medical Review Board of Gifu University, a total of 71 participants were recruited (22; healthy volunteers, 29; localized RCC and 20; RCC patients with metastasis or recurrence). Serum PD-1 levels were determined using PD-1 Human ELISA Kit (Thermo Fisher Scientific Inc., MA, USA). For Nivolumab-based ELISA, a capture antibody included in the kit was changed to Nivolumab. Nivolumab was coated to 96-well microplates using a commercially available kit. Results: Medians of the serum PD-1 levels measured by conventional ELISA were 31.8, 29.8 and 34.3 pg/ml in healthy volunteers, localized RCC patients and those with metastasis or recurrence, respectively, which showed no statistically significant difference. When the same set of patients were analyzed by Nivolumab-based ELISA, medians were 24.6, 23.7 and 46.4 pg/ml and the serum PD-1 levels were significantly elevated in patients with metastasis or recurrence (P = 0.013) compared to controls and localized patients. Of the 29 localized patients, 3 patients with relatively higher serum PD-1 levels at initial diagnosis relapsed later. Among 6 patients with metastasis who were treated with Nivolumab, well responders showed relatively lower serum PD-1 levels before treatment. Conclusion: The serum PD-1 levels determined using Nivolumab were increased in advanced RCC patients. Our results suggest that the detection of target molecules using a therapeutic antibody may yield more clinically relevant information, thus providing a novel approach to develop companion diagnostics. Citation Format: Kosuke Mizutani, Kengo Horie, Taku Kato, Keita Nakane, Kyojiro Kawakami, Yasunori Fujita, Masafumi Ito. Nivolumab-based ELISA revealed increased serum PD-1 levels in advanced RCC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3973.