An attenuated lymphocytic choriomeningitis virus vector enhances tumor control in mice partly via IFN-I
Young Rock Chung, Bakare Awakoaiye, Tanushree Dangi, Nahid Irani, Slim Fourati, Pablo Penaloza-MacMaster
Young Rock Chung, Bakare Awakoaiye, Tanushree Dangi, Nahid Irani, Slim Fourati, Pablo Penaloza-MacMaster
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Research Article Immunology

An attenuated lymphocytic choriomeningitis virus vector enhances tumor control in mice partly via IFN-I

Abstract

Viral vectors are being used for the treatment of cancer. Yet, their efficacy varies among tumors and their use poses challenges in immunosuppressed patients, underscoring the need for alternatives. We report striking antitumoral effects by a nonlytic viral vector based on attenuated lymphocytic choriomeningitis virus (r3LCMV). We show in multiple tumor models that injection of tumor-bearing mice with this vector results in improved tumor control and survival. Importantly, r3LCMV improved tumor control in immunodeficient Rag1–/– mice and MyD88–/– mice, suggesting that multiple pathways contributed to the antitumoral effects. The antitumoral effects of r3LCMV were also observed when this vector was administered several weeks before tumor challenges, suggesting the induction of trained immunity. Single-cell RNA sequencing analyses, antibody blockade experiments, and knockout models revealed a critical role for host-intrinsic IFN-I in the antitumoral efficacy of r3LCMV vectors. Collectively, these data demonstrate potent antitumoral effects by r3LCMV vectors and unveil multiple mechanisms underlying their antitumoral efficacy.

Authors

Young Rock Chung, Bakare Awakoaiye, Tanushree Dangi, Nahid Irani, Slim Fourati, Pablo Penaloza-MacMaster

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Figure 1

r3LCMV replicates in B16 tumors and improves tumor control.

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r3LCMV replicates in B16 tumors and improves tumor control. (A) Experime...
(A) Experiment outline for evaluating whether r3LCMV improves tumor control. (B) Representative immunofluorescence staining in tumor sections at day 4 after treatment. We used an LCMV nucleoprotein-specific antibody (clone VL4) to label virus-infected cells in tumor sections. Scale bars: 200 μm. (C) Tumor control. (D) Representative FACS plots showing LCMV-specific CD8+ T cell responses at day 7 after treatment (gated on live CD8+ T cells). TILs, tumor-infiltrating lymphocytes. Mice were treated intratumorally with 2 × 105 focus-forming units (FFU) of r3LCMV, 5 days after subcutaneous tumor challenge. Before r3LCMV treatments, groups were distributed evenly according to tumor size. Data are pooled from 2 experiments (one experiment with n = 5 per group and another with n = 7 per group). Error bars represent SEM. Indicated P values were calculated by the Mann-Whitney test.