{
    "abstract": "Combination therapy has emerged as a leading trend in cancer treatment, having had a significant impact on the management of advanced-stage breast cancer. This approach, which relies on immune checkpoint modulation, has revolutionized the therapeutic landscape. However, the precise mechanisms underlying its therapeutic effects remain unclear.\nPreviously, we designed a bispecific antibody (BsAb) targeting PD-L1 (programmed cell death ligand 1) and the T cell immune checkpoint, LAG-3 (lymphocyte activation gene-3). In the present study, we evaluated the combination treatment of the BsAb (named Ba-PL) with doxorubicin (DOX) in a tumor-bearing mouse model and comprehensively investigated the underlying mechanisms involved.\nThe animal experiments demonstrated that the Ba-PL exerted an anti-tumor effect. Notably, mice treated with a combination of Ba-PL and DOX exhibited superior antitumor responses, mediated by the induction of robust immune cytokine responses. Furthermore, our findings revealed that this combination therapy restored depleted T cell activity and reinstated immune surveillance against tumors by reducing regulatory T cell levels. This immunotherapy combination exhibited favorable safety profiles and effectively prolonged the survival of tumor-bearing mice.\nBlocking PD-L1 and LAG-3 in combination with doxorubicin is therapeutic potential approach for breast cancer and offers hope for improved patient outcomes.",
    "authors": [
        {
            "affiliation": "National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.",
            "firstname": "Chenxing",
            "initials": "C",
            "lastname": "Zhang"
        },
        {
            "affiliation": "National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.",
            "firstname": "Jiaxin",
            "initials": "J",
            "lastname": "Liu"
        },
        {
            "affiliation": "National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.",
            "firstname": "Tiejun",
            "initials": "T",
            "lastname": "Gu"
        },
        {
            "affiliation": "National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.",
            "firstname": "Xiangyu",
            "initials": "X",
            "lastname": "Meng"
        },
        {
            "affiliation": "National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.",
            "firstname": "Xiaoyi",
            "initials": "X",
            "lastname": "Cai"
        },
        {
            "affiliation": "National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.",
            "firstname": "Jinfeng",
            "initials": "J",
            "lastname": "Zhang"
        },
        {
            "affiliation": "National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.",
            "firstname": "Yan",
            "initials": "Y",
            "lastname": "Chen"
        },
        {
            "affiliation": "Department of Orthopaedic, The First Hospital of Jilin University, Changchun, China. zhangdg@jlu.edu.cn.",
            "firstname": "Daguang",
            "initials": "D",
            "lastname": "Zhang"
        },
        {
            "affiliation": "National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China. ygwu@jlu.edu.cn.",
            "firstname": "Yongge",
            "initials": "Y",
            "lastname": "Wu"
        }
    ],
    "conclusions": "Blocking PD-L1 and LAG-3 in combination with doxorubicin is therapeutic potential approach for breast cancer and offers hope for improved patient outcomes.",
    "copyrights": "\u00a9 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",
    "doi": "10.1007/s10549-025-07676-9\n10.1158/1055-9965.EPI-20-1193\n10.3322/caac.21763\n10.1158/2159-8290.CD-18-1177\n10.3390/ph14080763\n10.1016/j.semcancer.2019.12.003\n10.1056/NEJMoa1809615\n10.1016/S0140-6736(20)32531-9\n10.1093/annonc/mdx708\n10.1080/14728222.2021.2006187\n10.1097/CJI.0000000000000281\n10.18632/oncotarget.7235\n10.1158/1078-0432.CCR-22-1449\n10.1016/j.ymthe.2022.05.003\n10.1139/cjpp-2023-0358\n10.3389/fcvm.2020.00026\n10.1111/bph.16405\n10.1016/j.cell.2021.09.020\n10.1038/s41467-024-47096-9\n10.3923/ijp.2023.286.295\n10.3390/cancers14030510\n10.1007/s00109-024-02444-6\n10.1016/j.prp.2023.154711\n10.1093/intimm/dxad035\n10.1016/j.trecan.2023.07.015\n10.1016/j.intimp.2024.111934\n10.1016/j.immuni.2018.05.006\n10.1158/1078-0432.CCR-23-2274\n10.1186/s40001-023-01196-2\n10.55730/1300-0144.5567\n10.1080/1750743X.2024.2379230\n10.1016/j.cytogfr.2024.02.003\n10.1186/s12943-024-02183-9\n10.1016/j.intimp.2022.109130\n10.1007/s00403-024-03352-y\n10.3389/fimmu.2022.932265\n10.2174/2589977513666210707114520\n10.3389/fonc.2024.1325575",
    "journal": "Breast cancer research and treatment",
    "keywords": [
        "Breast cancer",
        "Combination therapy",
        "DOX",
        "LAG-3",
        "PD-L1",
        "Tumor immunotherapy"
    ],
    "methods": null,
    "publication_date": "2025-03-07",
    "pubmed_id": "40050525\n30679171\n34451860\n31883913\n30345906\n33278935\n29092013\n34763593\n31219973\n26859684\n36342102\n35526096\n38039515\n32258060\n39617007\n34624224\n38555305\n35158779\n38600305\n37494802\n37837615\n37598003\n38574701\n30054205\n38060202\n37393300\n36945923\n39155854\n38431507\n39614288\n35969896\n39276195\n35967358\n34238181\n39534095",
    "results": "The animal experiments demonstrated that the Ba-PL exerted an anti-tumor effect. Notably, mice treated with a combination of Ba-PL and DOX exhibited superior antitumor responses, mediated by the induction of robust immune cytokine responses. Furthermore, our findings revealed that this combination therapy restored depleted T cell activity and reinstated immune surveillance against tumors by reducing regulatory T cell levels. This immunotherapy combination exhibited favorable safety profiles and effectively prolonged the survival of tumor-bearing mice.",
    "title": "Enhanced antitumor efficacy of bispecific antibody blocking PD-L1 and LAG-3 with doxorubicin: mechanism and safety evaluation.",
    "xml": "<Element 'PubmedArticle' at 0x788503c276f0>"
}