Abstract 5006: Comprehensive gene expression analysis of the tumor microenvironment in patients with advanced cancer treated with a personalized neoantigen vaccine, NEO-PV-01, in combination with anti-PD1
Authors: Bushway Meghan E. , Ting Ying Sonia , Besada Rana H. , Sciuto Tracey E. , Prabhakara Jasmina , Scherer Julian , Balogh Kristen N. , Lamb April , Kaplan Jennifer A. , Cleary Lisa D. , Moles Melissa A. , Church Sarah E. , Ren Yuqi , Ren Xing , Gaynor Richard B. , Goldstein Matthew J. , Brail Les H. , Greshock Joel , Srinivasan Lakshmi 
Published: August 2019

Background: Neoantigens arise from DNA mutations in cancer cells and are important targets for T cell mediated anti-tumor immunity. NEO-PV-01 is a personal neoantigen vaccine of up to 20 peptides designed based on a patient’s neoantigen and HLA profile that is directed at inducing tumor-specific T cell responses to neoantigens. Here we report comprehensive immune-related gene expression analysis of longitudinal tumor biopsies from patients with metastatic melanoma, bladder, and non-small cell lung cancer treated on our NT-001 trial with NEO-PV-01 + adjuvant in combination with nivolumab (NCT02897765) to correlate with clinical outcomes.

Methods: Tumor biopsies from all three tumor types were collected i) prior to treatment, ii) after 12 weeks of nivolumab monotherapy and iii) after completion of NEO-PV-01 vaccination. Targeted gene expression analysis on RNA extracted from FFPE blocks was performed using the NanoString™ nCounter platform. A custom set of 800 genes included markers for immune cell populations, cytolytic markers, immune activation and suppression, and the tumor microenvironment. Gene signatures of key immune features were calculated after normalization with housekeeping genes and used for subsequent analysis.

Results: Changes in the immune cell populations and the tumor microenvironment were detected after treatment with nivolumab and NEO-PV-01. Increases in various immune cell subsets, including T cells and B cells, as well as an increase in cytolytic phenotype were observed in tumor biopsies following treatment. Moreover, changes in the tumor microenvironment, consistent with the absence of tumor by histologic evaluation, were detected in many of the post-vaccination biopsies. In addition, these observations were consistent with data from peripheral blood that demonstrated durable de novo neoantigen-specific immune responses after vaccination. Additional exploratory analyses of the data demonstrate differential gene expression in patients’ tumors that align with tumor responses to therapy.

Conclusion: Treatment with nivolumab and NEO-PV-01 leads to changes in the tumor microenvironment that are consistent with cell types and phenotypes that could contribute to an anti-tumor response.

Citation Format: Meghan E. Bushway, Ying Sonia Ting, Rana H. Besada, Tracey E. Sciuto, Jasmina Prabhakara, Julian Scherer, Kristen N. Balogh, April Lamb, Jennifer A. Kaplan, Lisa D. Cleary, Melissa A. Moles, Sarah E. Church, Yuqi Ren, Xing Ren, Richard B. Gaynor, Matthew J. Goldstein, Les H. Brail, Joel Greshock, Lakshmi Srinivasan. Comprehensive gene expression analysis of the tumor microenvironment in patients with advanced cancer treated with a personalized neoantigen vaccine, NEO-PV-01, in combination with anti-PD1 [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 5006.