Personalized dendritic cell vaccine in multimodal individualized combination therapy improves survival in high-risk pediatric cancer patients

Int J Cancer. 2024 Oct 15;155(8):1443-1454. doi: 10.1002/ijc.35062. Epub 2024 Jul 3.

Abstract

A lot of hope for high-risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single-agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high-risk solid tumors using the N-of-1 approach in real-world scenario. A total of 160 evaluable events occurred in 48 patients during the 4-year follow-up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P = .048) or in patients with disease control (HR = 0.16, P = .00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P = .225). A strong synergistic effect was found for immune check-point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P = .0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents.

Keywords: N‐of‐1; cancer vaccine; immunotherapy; metronomic chemotherapy; rare cancer.

MeSH terms

  • Administration, Metronomic
  • Adolescent
  • Cancer Vaccines* / administration & dosage
  • Cancer Vaccines* / therapeutic use
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cyclophosphamide* / administration & dosage
  • Cyclophosphamide* / therapeutic use
  • Dendritic Cells* / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods
  • Infant
  • Male
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Neoplasms* / mortality
  • Neoplasms* / therapy
  • Precision Medicine* / methods
  • Vinblastine / administration & dosage
  • Vinblastine / therapeutic use

Substances

  • Cancer Vaccines
  • Cyclophosphamide
  • Vinblastine
  • Immune Checkpoint Inhibitors