| Summary: | Intratumoral (IT) myeloid dendritic cells (myDCs) play a pivotal role in re-licensing antitumor cytotoxic T lymphocytes. IT injection of the IgG<sub>1</sub> monoclonal antibodies ipilimumab and avelumab may induce antibody-dependent cellular cytotoxicity, thereby enhancing the release of tumor antigens that can be captured and processed by CD1c (BDCA-1)<sup>+</sup> myDCs. Patients with advanced solid tumors after standard care were eligible for IT injections of ≥1 lesion with ipilimumab (10 mg) and avelumab (40 mg) and intravenous (IV) nivolumab (10 mg) on day 1, followed by IT injection of autologous CD1c (BDCA-1)<sup>+</sup> myDCs on day 2. IT/IV administration of ipilimumab, avelumab, and nivolumab was repeated bi-weekly. Primary objectives were safety and feasibility. Nine patients were treated with a median of 21 × 10<sup>6</sup> CD1c (BDCA-1)<sup>+</sup> myDCs, and a median of 4 IT/IV administrations of ipilimumab, avelumab, and nivolumab. The treatment was safe with mainly injection-site reactions, but also immune-related pneumonitis (<i>n</i> = 2), colitis (<i>n</i> = 1), and bullous pemphigoid (<i>n</i> = 1). The best response was a durable partial response in a patient with stage IV melanoma who previously progressed on checkpoint inhibitors. Our combinatorial therapeutic approach, including IT injection of CD1c (BDCA-1)<sup>+</sup> myDCs, is feasible and safe, and it resulted in encouraging signs of antitumor activity in patients with advanced solid tumors.
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