{
  "abstract": "Background Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising clinical activity in several solid tumor types. However, the efficacy of TIL therapy is often limited by immunosuppressive mechanisms within the tumor microenvironment (TME), and the physical barriers imposed by the tumor stroma. These challenges are especially pronounced in cold tumors characterized by low immune infiltration, restricting the broader application of TIL therapy across diverse solid tumor indications.Methods To address these challenges, we developed RD213, a next-generation TIL product genetically engineered to secrete a bispecific T cell engager (BiTE) targeting a tumor-associated antigen expressed on both tumor cells and the surrounding stroma, with minimal expression in normal tissues. This dual targeting strategy enhances TIL penetration through fibroblast-rich stromal barriers and promotes recruitment of endogenous peripheral T cells, leading to deeper immune infiltration and synergistic tumor control. Multiple vector designs were evaluated, and RD213 was selected as the lead candidate based on stable BiTE expression and optimal T cell function.Results RD213 was successfully manufactured using our proprietary StemTexp® and StaViral® platforms, preserving a favorable memory phenotype without inducing excessive activation or exhaustion. In vitro assays revealed that RD213 exhibited significantly enhanced cytotoxicity and cytokine production in co-culture with tumor cells, outperforming conventional TILs in serial killing assays. Notably, the BiTE secreted by RD213 also activated PBMC-derived T cells, enabling persistent and effective serial tumor cell killing. In vivo, RD213 demonstrated superior anti-tumor efficacy in NOG mice bearing HLA-matched tumors, accompanied by increased TIL infiltration and enhanced effector function within the TME.Conclusions These findings highlight RD213 as a promising approach to overcoming key limitations of traditional TIL therapy. By enhancing tumor infiltration and harnessing both engineered and endogenous T cells, RD213 represents a novel TIL-based therapeutic strategy for the treatment of refractory solid tumors. Clinical development of RD213 is currently underway.",
  "authors": [
    {
      "affiliations": [
        "Grit Biotechnology Inc, Shanghai, China"
      ],
      "name": "Jingwei Sun"
    },
    {
      "affiliations": [
        "Grit Biotechnology Inc, Shanghai, China"
      ],
      "name": "Yiyang Tan"
    },
    {
      "affiliations": [
        "Grit Biotechnology Inc, Shanghai, China"
      ],
      "name": "Jiahui Jin"
    },
    {
      "affiliations": [
        "Grit Biotechnology Inc, Shanghai, China"
      ],
      "name": "Jingman Wang"
    },
    {
      "affiliations": [
        "Grit Biotechnology Inc, Shanghai, China"
      ],
      "name": "Fengbiao Guo"
    },
    {
      "affiliations": [
        "Grit Biotechnology Inc, Shanghai, China"
      ],
      "name": "Zhao Xu"
    },
    {
      "affiliations": [
        "Grit Biotechnology Inc, Shanghai, China",
        "University of Southern California, Los Angeles, CA, USA"
      ],
      "name": "Pin Wang"
    },
    {
      "affiliations": [
        "Grit Biotechnology Inc, Shanghai, China"
      ],
      "name": "Yarong Liu"
    }
  ],
  "title": "385 A bispecific engager-secreting TIL therapy designed to penetrate stromal barriers and boost tumor killing in solid tumors",
  "uid": "ffb909d3-9047-5d8e-9c9a-910ea3ccfb52"
}