Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy

Anguille, SÃ©bastien; Smits, Evelien; Bryant, Christian; Acker, Heleen H. Van; Goossens, Herman; Lion, Eva; Fromm, Phillip D.; Hart, Derek N. J.; Tendeloo, Viggo F. Van; Berneman, Zwi N.

doi:10.1124/pr.114.009456

Cited by 131 publications

(143 citation statements)

References 282 publications

(396 reference statements)

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“…6, 13 The precise mechanisms underlying the anticancer synergy between tumor vaccines and chemotherapy are currently being investigated 41 ; 1 potential mechanism involves the release of cytokines (eg, TNF-a) by vaccineinduced CD8…”

Section: Discussionmentioning

confidence: 99%

“…12 In view of their role as the most potent antigenpresenting cells of the immune system, dendritic cells (DCs) are eminently equipped to stimulate antigen-specific T-cell immunity. 13 This explains the strong interest in the use of these cells for cancer vaccination strategies. 14 The aim of this phase 2 study was to determine the clinical efficacy of DC vaccine therapy in AML and, more specifically, whether this form of immunotherapy can be applied in the adjuvant setting to decrease the risk of relapse after chemotherapy and improve survival.…”

Section: Introductionmentioning

confidence: 99%

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Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia

Anguille

Velde

Smits

et al. 2017

Blood

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169

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Key Points• WT1 mRNA-electroporated DCs can prevent or delay relapse in 43% of patients with AML in remission after chemotherapy.• OS compares favorably with the new survival data from the Swedish Acute Leukemia Registry and correlates with molecular and WT1-specific CD8 1 T-cell responses.Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P 5 .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age £65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8 1 T cells. Long-term OS was correlated with interferon-g 1 and tumor necrosis factor-a 1 WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8 1 T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8 1 T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224. (Blood. 2017;130(15):1713-1721

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia

Anguille

Velde

Smits

et al. 2017

Blood

Self Cite

169

146

View full text Add to dashboard Cite

show abstract

“…DC-based immunotherapy aims to treat various types of cancer or, in some cases [40,41], human immunodeficiency virus (HIV) infection by eliciting and boosting a patient's immunity against diseased cells and, hence, they are often called DC vaccines. Production of a DC therapy frequently involves harvesting monocytes from the patient, differentiating them into mature DCs and then loading the cells with tumor antigens, resulting in a final product [42]. Loading of the cells with disease antigens occurs by a variety of different payload delivery methods: incubation with lysed or apoptotic cancer cells; fusion with live, irradiated cancer cells; and electroporation with disease antigen peptide or its encoding messenger RNA [42].…”

Section: Cryopreserved Dcs In Clinical Trialsmentioning

confidence: 99%

Preservation of cell-based immunotherapies for clinical trials

Johnson

et al. 2019

Cytotherapy

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“…Известно, что ДК должны от-вечать целому ряду требований, которые отражают их способность презентации антигенов и стимуля-ции Т-клеток, быть жизнеспособными, экспрессиро-вать высокий уровень маркеров зрелости, костиму-ляторных молекул и молекул адгезии, секретировать цитокины, активировать ЦТЛ и Тh1 -опосредство-ванный иммунный ответ [10].…”

Section: обоснование исследованияunclassified