{
  "abstract": "Background Multiple myeloma (MM) is a hematologic malignancy characterized by a high relapse rate despite recent therapeutic advances. B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D) are two well-validated targets, with Food and Drug Administration-approved bispecific antibodies demonstrating clinical efficacy; however, their effectiveness is often limited by antigen escape and immune evasion.Methods This study presents a novel humanized trispecific antibody, YMN-V115, designed in a 1+1+1 format with one binding site each for BCMA, GPRC5D, and CD3. This structural configuration was strategically selected to maximize tumor-specific T cell engagement through dual-antigen targeting while minimizing the risk of CD3-mediated off-tumor toxicity.Results YMN-V115 exhibited superior cytotoxic activity against MM cells in both in vitro and in vivo models, outperforming its bispecific counterparts. Notably, its efficacy was maintained under soluble BCMA-saturated conditions, demonstrating resistance to decoy inhibition. Moreover, YMN-V115 effectively addressed antigenic heterogeneity by targeting both BCMA + and GPRC5D+ tumor subsets, resulting in enhanced T-cell activation and durable tumor control.Conclusions YMN-V115 represents a next-generation trispecific T-cell engager that effectively addresses antigenic heterogeneity and immune evasion in MM. These preclinical findings support its further clinical development as a promising therapeutic strategy for relapsed or refractory MM.",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Jia Li"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Qizhong Lu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Zhixiong Zhu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Xuehui Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Yangji Chen"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Zongliang Zhang"
    },
    {
      "affiliations": [
        "Department of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Zhengyu Yu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Zeng Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Yongdong Chen"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Hai Xie"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Nian Yang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Huaqing Lu"
    },
    {
      "affiliations": [
        "Department of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Ting Niu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Chunlai Nie"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China",
        "Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan, China"
      ],
      "name": "Aiping Tong"
    },
    {
      "affiliations": [
        "State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China"
      ],
      "name": "Hexian Li"
    }
  ],
  "title": "YMN-V115: a novel humanized BCMA/GPRC5D/CD3 trispecific antibody in relapsed/refractory multiple myeloma",
  "uid": "43f305cb-7c51-5adf-bfdf-94c708b7054a"
}