{
  "abstract": "Background Oncolytic virotherapy represents a promising anticancer strategy by combining direct tumor lysis with in situ immune activation. However, its efficacy remains limited in immune-cold tumors, which are characterized by poor T-cell infiltration and an immunosuppressive microenvironment. Although engineering oncolytic viruses to deliver chemokines has been explored to modulate immune recruitment, most existing approaches activate only a single immune axis. Senecavirus A (SVA), a tumor-selective RNA virus with high genetic stability and flexible transgene capacity, offers an attractive platform for coordinated intratumoral delivery of immune payloads.Methods We engineered recombinant SVA vectors to achieve co-expression of CXCL11 and vXCL1 within tumor, aiming to synergistically recruit both T cells and cross-presenting dendritic cells and remodel the tumor immune landscape. In vitro and in vivo assays were conducted to assess viral properties (stability, replication kinetics, gene expression) and cytotoxicity against B16-F10 melanoma cells in different stages, with tumor burden, immune cell infiltration, and mouse survival in C57BL/6 mice analyzed to evaluate the overall therapeutic efficacy.Results Signal-peptide deletion significantly improved the genetic stability of transgenes and enhanced intratumoral payload retention, without compromising viral fitness. In murine models, CXCL11-expressing virus monotherapy achieved enhanced tumor control, prolonged survival, and provided preliminary evidence suggestive of protection on tumor rechallenge. Furthermore, the combination of CXCL11 and vXCL1 further augmented dendritic cell activation, promoted CD8 + T cell infiltration, and shifted macrophages toward an M1-polarized phenotype, while sustaining higher intratumoral viral loads. These coordinated immune changes led to deeper and more durable tumor regression.Conclusions Our findings validate the combination of CXCL11- and vXCL1-armed SVA as a potent immunovirotherapy strategy and propose a design principle for multistage, multigene intervention: concurrently targeting leukocyte recruitment, antigen presentation, and effector activation provides complementary mechanisms that synergistically amplify therapeutic efficacy.",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Wenjie Li"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Jingshuai Sun"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Hanchen Tian"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Xiaoyu Tang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Long Gao"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Shuangshuang Liang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Zhuofan Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Yuan Sun"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Jingyun Ma"
    },
    {
      "affiliations": [
        "State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou, Guangdong, China",
        "College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China"
      ],
      "name": "Xiaoya Zhao"
    }
  ],
  "title": "Dual-chemokine-armed oncolytic Senecavirus A co-recruits cDC1 and CXCR3+ T cells to convert ‘cold’ melanoma and drive durable regression",
  "uid": "bd525854-72ae-5170-9773-c91cea7213d0"
}