Abstract 4208: In situ vaccination of non-small cell lung cancer with CXCL9/10-engineered dendritic cells combined with PD-1 blockade

Abstract

Abstract Lung cancer is the most common cause of cancer death worldwide with approximately 85% of patients having non-small cell lung cancer (NSCLC). Checkpoint blockade immunotherapy has evolved the current treatment landscape with robust and durable responses in approximately 20% of patients with progressive, locally advanced or metastatic NSCLC, as well as in treatment-naïve advanced disease. Inefficient tumor antigen presentation, diminished T cell infiltration into tumor and LKB1-inactivating mutations contribute to the mechanisms of resistance to programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1) blockade in NSCLC. LKB1 deficiency also facilitates an immunosuppressive environment that promotes tumor growth. One approach to overcome this immunosuppressive tumor microenvironment (TME) is to utilize in situ vaccination with gene-modified functional antigen presenting cells (APCs) to enhance tumor antigen presentation and promote tumor-specific T cell activation. It has been shown that the chemokines CXCL9 and CXCL10 (CXCL9/10) are important signaling molecules secreted by CD103+ dendritic cells (DCs) to orchestrate the anti-tumor immunity. Thus, we hypothesize that intratumoral (IT) injection of CXCL9/10-secreting DCs (CXCL9/10-DCs) can potentiate the response to anti-PD-1 monotherapy in LKB1-deficient NSCLC by promoting antigen presentation and inducing T cell infiltration. Our preliminary data shows that CXCL9/10-DC injection modulates systemic immunity and generates anti-tumor responses that are augmented by the combination treatment with anti-PD1. In an in vivo murine model of Lkb1-null lung cancer bearing high tumor mutational burden (TMB), CXCL9/10-DC facilitates recruitment of effector T cells into the TME and tumor-specific T cell activation. These studies will enhance our understanding of anti-tumor immunity mediated by in situ DC vaccination and facilitate the improvement of novel vaccine therapies. B. Liu and S. M. Dubinett contributed equally to this work. Citation Format: Raymond J. Lim, Ramin Salehi-rad, Linh M. Tran, Camelia Dumitras, Jensen W. Abascal, William P. Crosson, Tejas S. Patel, Samantha Man, Rui Li, Kostyantyn Krysan, Bin Liu, Steven M. Dubinett. In situ vaccination of non-small cell lung cancer with CXCL9/10-engineered dendritic cells combined with PD-1 blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4208.