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

M. Kyr, P. Mudry, K. Polaskova, LZ. Dubska, R. Demlova, J. Kubatova, E. Hlavackova, KC. Pilatova, P. Mazanek, K. Vejmelkova, V. Dusek, P. Tinka, M. Balaz, T. Merta, Z. Kuttnerova, T. Turekova, Z. Pavelka, P. Pokorna, H. Palova, M. Mlnarikova, M....

. 2024 ; 155 (8) : 1443-1454. [pub] 20240703

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24018706

Grantová podpora
LM2023049 Ministerstvo Školství, Mládeže a Tělovýchovy
MUNI/A/1395/2022 Ministerstvo Školství, Mládeže a Tělovýchovy
MUNI/A/1625/2023 Ministerstvo Školství, Mládeže a Tělovýchovy
LX22NPO5102 Ministerstvo Školství, Mládeže a Tělovýchovy
101059788 HORIZON EUROPE
65269705 Ministerstvo Zdravotnictví České Republiky, FNBr
NV19-03-00562 Ministerstvo Zdravotnictví České Republiky, FNBr

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.

Citace poskytuje Crossref.org

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$a 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.
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