Intratumoral DC1 (type 1 dendritic cell) immunotherapy + dual HER2 blockade drives 89% pCR in HR−/HER2+ early breast cancer

IT DC1 is an intratumoral conventional type 1 dendritic-cell (cDC1/DC1) therapy intended to inflame the tumor microenvironment; in the single-arm Phase 2 NATASHA trial (NCT05325632), patients with stage I–III HER2+ breast cancer and tumors ≥1cm received weekly IT DC1 ×6 (100M cells) with trastuzumab/pertuzumab (HP) starting day 1, then weekly paclitaxel ×12 with continued HP (n=47 enrolled; 42 had surgery by January 22, 2026). pCR was 50% in HR+/HER2+ (12/24) and 89% in HR−/HER2+ (16/18); for comparison, neoadjuvant paclitaxel+HP (THP) typically yields ~42% pCR in HR+ and ~85% in HR− disease (so HR− here looks in-family with strong THP benchmarks, while HR+ looks a bit higher than many THP-only reports but still within the broader real-world range). DC1-related toxicity was mostly grade 1/2 flu-like symptoms and injection-site reactions; correlative work showed increased intratumoral CD3+ T-cell infiltration and reduced tumor cells by multiplex IF, and ctDNA was positive in 64% (16/25) at baseline with clearance in 14/16—most (13/16) clearing after DC1+HP and before chemotherapy (median post-surgery follow-up 15.1 months; no recurrences reported so far).