Abstract 3813: MPF as a monitoring biomarker for a mesothelin-targeted therapy against malignant mesothelioma and other cancer

Abstract

Introduction: Tumor antigen mesothelin had been shown to be elevated in mesothelioma, ovarian, pancreatic, and lung cancer. The mesothelin gene encodes a precursor protein of 69 kDa, which is cleaved into a 31 kDa soluble megakaryocyte potential factor (MPF), and a cell membrane-bound 40 kDa mesothelin. There is a high degree of interest in targeting mesothelin for mesothelioma and other cancers with various antibody-based agents, and some successes in early stage clinical trials with some of the agents. For the development of these targeted therapeutics, specific biomarkers would be needed for monitoring treatment responses, and detecting and evaluating tumor progression. The current test that detects mesothelin is not suitable due to the antigen-binding from the therapeutic antibodies. There is an urgent need to develop and validate an alternative test to support these clinical trials and for disease management.

Methods: Using ECLIA technology and proprietary antibody reagents, we developed a new test for the cleaved MPF polypeptide. We further conducted comprehensive analytical and clinical validation of the test according to the guidelines for tumor antigen tests. Using samples from a retrospective clinical trial with an anti-mesothelin immunotoxin and the standard 1st line chemotherapeutic agents for newly diagnosed malignant mesothelioma patients, we examined the effectiveness of the test for treatment monitoring of the investigational therapy.

Results: Our data gives a strong validation for the analytical and clinical performances of MPF test. While no other current test has been proven to be able to monitor response of mesothelioma to systemic therapies, our data provides the proof of clinical effectiveness for MPF test. In the patients with the elevated tumor antigen, there is a specific and highly significant reduction of MPF at the end of each treatment cycle for a total of 6 cycles in the patients with objective response. Later, about half of these patients with objective response and MPF reduction regained the levels of MPF at the time of disease progression.

Conclusion: The study indicates that MPF test is effective in monitoring the treatment response to systemic therapies for mesothelioma patients with elevated MPF. It may also provide pivotal information on the expression of target mesothelin protein when tumors progress.

Citation Format: Yunkai Yu, Raffit Hassan, Jingli Zhang, Masanori Onda, Ira Pastan, Liang Cao. MPF as a monitoring biomarker for a mesothelin-targeted therapy against malignant mesothelioma and other cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3813. doi:10.1158/1538-7445.AM2017-3813