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Article

Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review)

  • Authors:
    • Yang Zheng
    • Yangxuan Ding
    • Longxia Chen
    • Zengrui Zhang
    • Ruilin Ding
  • View Affiliations / Copyright

    Affiliations: Clinical Trial Center, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Clinical Medical School, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Clinical Research Ethics Committee, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
  • Article Number: 124
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    Published online on: July 25, 2025
       https://doi.org/10.3892/or.2025.8956
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Abstract

Cancer has become one of the leading causes of death in most countries. While immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics by harnessing antitumor immunity, their clinical application is constrained by intrinsic resistance in most patients and limited responsiveness across specific tumor types. Rational combination strategies may enhance therapeutic outcomes. Antibody‑drug conjugates (ADCs) are an optimal therapeutic partner for synergistic combination with ICIs. ADCs enhance ICI efficacy by inducing immunogenic cell death, which activates tumor‑specific immune responses, remodeling the immunosuppressive tumor microenvironment, and amplifying ICI‑mediated immune cell activation. ADC‑ICI combinations have encouraging antitumor activity across multiple types of solid malignancies. The present review systematically evaluates the synergistic potential of ADC and ICI combination in solid tumor management.
View Figures

Figure 1

Rationale for combining ADCs and
ICIs. ADC cytotoxic payloads induce ICD, releasing DAMPs. Combined
with direct payload effects, DAMPs drive DCs maturation in tumors.
Payloads facilitate DC migration to lymphoid tissues, enhancing T
cell activation, tumor infiltration, and immune memory. (4) ADC treatment upregulates PD-L1 and
MHC-I, potentially sensitizing tumors to ICIs. (5) The antibody mediates ADCC, activating
innate immunity. ICD, immunogenic cell death; DAMP,
danger-associated molecular pattern; DC, dendritic cell; TME, tumor
microenvironment; MHC I, major histocompatibility complex class I;
ADCC, antibody-dependent cellular cytotoxicity; ADC, antibody-drug
conjugate; ICI, immune checkpoint inhibitor; TCR,; PD-L1,
programmed death ligand-1; NK, Natural killer; FCγRIII, Fcγ
receptor III.
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Spandidos Publications style
Zheng Y, Ding Y, Chen L, Zhang Z and Ding R: Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review). Oncol Rep 54: 124, 2025.
APA
Zheng, Y., Ding, Y., Chen, L., Zhang, Z., & Ding, R. (2025). Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review). Oncology Reports, 54, 124. https://doi.org/10.3892/or.2025.8956
MLA
Zheng, Y., Ding, Y., Chen, L., Zhang, Z., Ding, R."Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review)". Oncology Reports 54.4 (2025): 124.
Chicago
Zheng, Y., Ding, Y., Chen, L., Zhang, Z., Ding, R."Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review)". Oncology Reports 54, no. 4 (2025): 124. https://doi.org/10.3892/or.2025.8956
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng Y, Ding Y, Chen L, Zhang Z and Ding R: Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review). Oncol Rep 54: 124, 2025.
APA
Zheng, Y., Ding, Y., Chen, L., Zhang, Z., & Ding, R. (2025). Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review). Oncology Reports, 54, 124. https://doi.org/10.3892/or.2025.8956
MLA
Zheng, Y., Ding, Y., Chen, L., Zhang, Z., Ding, R."Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review)". Oncology Reports 54.4 (2025): 124.
Chicago
Zheng, Y., Ding, Y., Chen, L., Zhang, Z., Ding, R."Breaking therapeutic barriers in solid tumors: Clinical progress of antibody‑drug conjugate/immune checkpoint inhibitor combinations (Review)". Oncology Reports 54, no. 4 (2025): 124. https://doi.org/10.3892/or.2025.8956
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