ArticleCancer research communications2026
Advanced CD276-Targeting Dual-Payload Antibody-Drug Conjugates for Cancer Therapy.
Article in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Antibody-drug conjugate (ADC) represents an effective therapeutic strategy for cancer, leveraging a cancer-targeting monoclonal antibody (mAb) linked to a potent payload. In this study, we report novel dual-payload ADCs (DualADC), which harness one antibody to simultaneously deliver chemotherapy and immunotherapy for aggressive triple-negative breast cancer (TNBC). Specifically, we developed two-site, that is, cysteine and lysine, co-conjugation technologies to link a chemotherapeutic agent for direct tumor cell killing and a Toll-like receptor dual agonist for tumoral immunity enhancement to our humanized anti-CD276 (B7-H3) mAb. Our antibody binds to TNBC with high affinity and selectivity while exhibiting minimal off-target effects in normal human tissues. Three DualADCs were fully characterized by validating the conjugations and quantifying the drug-to-antibody ratios and drug-to-drug ratio using several analytic tools. In vitro evaluations revealed a high cancer cell binding rate via flow cytometry, efficient drug internalization with confocal microscopy, and high anticancer cytotoxicity in three TNBC cell lines. In vivo investigations in two TNBC xenograft mouse models demonstrated that DualADC carrying deruxtecan and imidazoquinoline has the best antitumor efficacy, that is, favorable biodistribution in TNBC, high tumor burden reduction, low systemic toxicity, and upregulation of immune pathways. Collectively, this study establishes advanced dual-payload antibody-drug conjugation technologies and identifies a good DualADC candidate for cancer therapy. SIGNIFICANCE: Advanced dual-payload antibody-drug conjugation technologies were established, and a promising DualADC was developed for targeted cancer chemoimmunotherapy.
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