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Purpose <p>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.</p> Methods <p>Previously, 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.</p> Results <p>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.</p> Conclusion <p>Blocking PD-L1 and LAG-3 in combination with doxorubicin is therapeutic potential approach for breast cancer and offers hope for improved patient outcomes.</p>

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Enhanced antitumor efficacy of bispecific antibody blocking PD-L1 and LAG-3 with doxorubicin: mechanism and safety evaluation

  • 期刊论文

  • 发表日期：

    2025年3月6日

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  • Chenxing Zhang,
  • Jiaxin Liu,
  • Tiejun Gu,
  • Xiangyu Meng,
  • Xiaoyi Cai,
  • Jinfeng Zhang,
  • Yan Chen,
  • Daguang Zhang,
  • Yongge Wu

摘要

Purpose

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.

Methods

Previously, 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.

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.

Conclusion

Blocking PD-L1 and LAG-3 in combination with doxorubicin is therapeutic potential approach for breast cancer and offers hope for improved patient outcomes.