Antibody-Drug Conjugates Synergize with Agonist Anti-CD137 Monoclonal Antibodies in Solid Tumors.

In mouse solid tumor models, combining NECTIN-4 or HER2 ADCs (MMAE- or deruxtecan-conjugated) with agonist anti-CD137 produces synergistic antitumor effects.

• Why it matters: ADCs can reshape tumor stroma, but their immunologic impact may be amplified by pairing with immune costimulation rather than checkpoint blockade alone.
• What they did: The study tested ADCs against NECTIN-4 or HER2 together with anti-CD137 agonists in mice, measuring synergy, CD137 upregulation on intratumor CD8+ and CD4+ T cells, and dependence on cDC1 dendritic cells and CD8+ T cells.
• The result: ADC treatment induced immunogenic cell death with cDC1 cross-presentation and CD8+ T-cell cross-priming to become CD137-positive, enabling synergy even against concomitant lesions lacking ADC target expression.

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