{
  "abstract": "Background Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematological malignancies; however, it faces significant challenges in treating solid tumors, including limited immune infiltration into tumor tissues and immunosuppressive tumor microenvironment. Oncolytic viruses (OVs), which selectively destroy cancer cells and trigger antitumor immune responses, offer a compelling solution to these challenges. Newcastle disease virus (NDV) is a natural OV that exhibits antitumor activity with minimal side effects in clinical studies. We hypothesized that combining NDV, engineered to express a chemokine, with tetracycline-inducible CAR T cells could synergistically enhance CAR T cell therapy efficacy against solid tumors.Methods We constructed a recombinant NDV expressing human CCL19 (rNDV19) and evaluated its therapeutic efficacy alongside doxycycline-inducible CAR T cells in an orthotopic lung cancer mouse model. Tumor burden, immune cell infiltration, and mouse survival were analyzed.Results rNDV19 retained potent oncolytic activity, significantly reducing tumor cell viability while achieving stable expression of human CCL19. rNDV19 triggered significant recruitment of CAR T cells into tumors and promoted their activity. Mechanistic analysis revealed that rNDV19 and CAR T cell combination therapy remodeled the tumor microenvironment. Transcriptomic profiling highlighted activation of critical immune pathways—including leukocyte chemotaxis, T cell differentiation, cytokine production, and immune response-activating signaling in combination therapy. These findings were further corroborated by upregulated expression of T cell activation markers like IL-2, TNF-α, IFN-γ, and cytotoxic effector molecules such as granzyme A and perforin. Therapeutically, the combination synergistically extended median survival time from 22 to 36 days, outperforming monotherapies.Conclusions The combination of rNDV19 and CAR T cells represents a promising strategy for overcoming the limitations of CAR T cell therapy for solid tumors. This approach enhances immune cell infiltration and activation, potentially converting “cold” tumors into “hot” tumors to improve therapeutic outcomes and offering a robust translational framework for solid tumor immunotherapy.",
  "authors": [
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Man Liu"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Can Li"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Lan-Ting Feng"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Ren-Yu Zhang"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Wen-Liang Li"
    },
    {
      "affiliations": [
        "Department of Health Statistics, Fourth Military Medical University, Xi'an, China"
      ],
      "name": "Ling Wang"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Hai-Jiao Yang"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Qian Li"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Ze-Kun Liu"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Yu-Le Yong"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Xiang-Min Yang"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Hong-Yong Cui"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Ling-Min Kong"
    },
    {
      "affiliations": [
        "Department of Transfusion Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China"
      ],
      "name": "Wen Yin"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Zhi-Nan Chen"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Huijie Bian"
    },
    {
      "affiliations": [
        "Department of Cell Biology and National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China",
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, China"
      ],
      "name": "Ding Wei"
    }
  ],
  "title": "hCCL19-expressing recombinant Newcastle disease virus boosts CAR T cell infiltration and efficacy in solid tumor",
  "uid": "fda02580-1b60-5ed3-89cd-eefd33fead8c"
}