1. Personalized dendritic cell vaccine in multimodal individualized combination therapy improves survival in high-risk pediatric cancer patients.
- Author
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Kyr M, Mudry P, Polaskova K, Dubska LZ, Demlova R, Kubatova J, Hlavackova E, Pilatova KC, Mazanek P, Vejmelkova K, Dusek V, Tinka P, Balaz M, Merta T, Kuttnerova Z, Turekova T, Pavelka Z, Pokorna P, Palova H, Mlnarikova M, Jezova M, Kellnerova R, Kozakova S, Slaby O, Valik D, and Sterba J
- Subjects
- Humans, Male, Female, Child, Combined Modality Therapy, Child, Preschool, Adolescent, Administration, Metronomic, Immunotherapy methods, Vinblastine administration & dosage, Vinblastine therapeutic use, Infant, Immune Checkpoint Inhibitors therapeutic use, Follow-Up Studies, Dendritic Cells immunology, Cancer Vaccines administration & dosage, Cancer Vaccines therapeutic use, Neoplasms mortality, Neoplasms immunology, Neoplasms therapy, Neoplasms drug therapy, Precision Medicine methods, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage
- 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., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2024
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