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Intratumoral Combinatorial Administration of CD1c (BDCA-1)+ Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors

Journal Contribution - Journal Article

Subtitle:A Phase IB Clinical Trial

Intratumoral (IT) myeloid dendritic cells (myDCs) play a pivotal role in re-licensing antitumor cytotoxic T lymphocytes. IT injection of the IgG1 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)+ 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)+ 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 × 106 CD1c (BDCA-1)+ 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 (n = 2), colitis (n = 1), and bullous pemphigoid (n = 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)+ myDCs, is feasible and safe, and it resulted in encouraging signs of antitumor activity in patients with advanced solid tumors.

Journal: Vaccines
ISSN: 2076-393X
Issue: 4
Volume: 8
Pages: 1-16
Publication year:2020
Keywords:cancer immunotherapy, conventional dendritic cells, dendritic cells, immune checkpoint inhibitors, intratumoral, myeloid dendritic cells, tumor microenvironment
  • ORCID: /0000-0003-1688-8940/work/84594676
  • ORCID: /0000-0001-8337-5382/work/83993904
  • ORCID: /0000-0003-1255-8071/work/83993438
  • ORCID: /0000-0002-9945-4357/work/83993094
  • ORCID: /0000-0003-0658-5903/work/83991344
  • WoS Id: 000602208800001
  • Scopus Id: 85096622671
  • DOI: https://doi.org/10.3390/vaccines8040670
CSS-citation score:1
Accessibility:Open