Methods for generating the CD137L-DC-EBV-VAX anti-cancer vaccine

Methods Cell Biol. 2024:183:187-202. doi: 10.1016/bs.mcb.2023.07.002. Epub 2023 Sep 15.

Abstract

Dendritic cells (DC) are professional antigen presenting cells (APCs) that can efficiently present captured antigens to cytotoxic T cells and initiate powerful antigen-specific responses. Therefore, DC have been explored for cancer immunotherapy. However, due to the scarcity of DCs in the peripheral blood, ex-vivo expansion is required to generate sufficient DCs before use. The majority of DC-based tumor vaccines utilize monocyte-derived DC (mo-DC) that are generated with GM-CSF and IL-4. Here, we describe the generation of a novel type of DC, CD137L-DC, which are generated from monocytes by stimulation with a CD137 ligand agonist, and that proved to be more potent than classical mo-DC in inducing cytotoxic responses against tumor associated viruses, such as EBV and HBV in vitro. In a phase I clinical trial on patients with locally recurrent or metastatic NPC, a CD137L-DC-EBV vaccine showed good tolerability and prolonged patient survival, providing a basis for further development of CD137L-DC vaccines for immunotherapy.

Keywords: CD137L-DC; Cell preparation; Dendritic cell; GMP; Immunotherapy; Nasopharyngeal carcinoma.

MeSH terms

  • Cancer Vaccines* / therapeutic use
  • Dendritic Cells
  • Herpesvirus 4, Human
  • Humans
  • Monocytes
  • Neoplasms* / therapy

Substances

  • Cancer Vaccines