Abstract 660: Pre-symptomatic detection and early treatment of mammary cancer with anti-PD-L1 in a mouse mode
Authors: Duan Hu , Johnston Stephen Albert , Luhui Shen 
Published: July 2017

Abstract
Cancer kills ~8M people/year and the WHO predicts an epidemic of cancer in the developing world over the next 20 years due to increased longevity. Development of a simple method to detect and treat cancer early could be a solution to this challenge. Here we test this approach in principle in a transgenic mouse mammary tumor model by immunosignature (IMS) diagnostics. IMSs are profiles of antibodies in the blood displayed on a high density peptide array. As previous published data showed, the IMS can distinguish different diseases based on the disease specific antibody profile in the patient, including different cancers and infectious diseases. According to the immune surveillance theory, the immune system, including the humoral immune response, starts to interact with cancer cells as soon as they are transformed. First, we tested if the IMS is sensitive enough to detect the antibody profile change caused by the early tumor development in the FVB-NeuN (MMTVneu/202Mul/J) mammary cancer model. In the FVB-NeuN model, the MMTV promoter activates the wild type rat ERBB2 gene in mammary cells, and every mammary cell potentially can convert into a cancer cell. The transition from normal mammary glands to hyperplasia of FVB-NeuN in mouse starts at 8.6 to 15 weeks after birth. The mice develop the first palpable tumor in one of the ten mammary glands by 19-45 weeks of age with an average age of 32±1.2 weeks in our hands. We collected serum every 4 weeks from the FVB-NeuN mice and the wild type FVB mice for the IMS analysis. The IMS can distinguish the FVB-NeuN mouse from the age matched wild type FVB mouse as early as 12 weeks (Stage-1) before the onset of the first palpable tumor. We also analyzed the IMSs from the Stage-2 (8 weeks before the palpable tumor and so on) to Stage 4. Different IMS of each stage has only partial overlap with the other stages. The cross-stage prediction analysis showed the accuracy of the cancer detection by using different IMS is from 75% to 93%. Second, we determined if early treatment at the time of diagnosis with the checkpoint blockade, anti-PD-L1, would inhibit the tumor growth. A course of 3 injections at the time of diagnosis significantly retarded tumor growth relative to untreated controls. The early treatment elicited long-term protection which could restrict the tumor growth even four months after the treatment. The treated mice presented a specific IMS at 28 days post treatment and 35 days post the first palpable tumor, compared to the untreated mice. This indicates that the early treatment elicited an anti-tumor immune response that could inhibit tumor growth. This preliminary experiment suggests that early diagnosis combined with systemic treatment might be a method to control or eliminate cancer.
Citation Format: Hu Duan, Stephen Albert Johnston, Shen Luhui. Pre-symptomatic detection and early treatment of mammary cancer with anti-PD-L1 in a mouse mode [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 660. doi:10.1158/1538-7445.AM2017-660