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Immunological responses to adjuvant vaccination with combined CD1c⁺ myeloid and plasmacytoid dendritic cells in stage III melanoma patients.

ABSTRACT: We evaluated the immunological responses of lymph-node involved (stage III) melanoma patients to adjuvant dendritic cell vaccination with subsets of naturally occurring dendritic cells (nDCs). Fifteen patients with completely resected stage III melanoma were randomized to receive adjuvant dendritic cell vaccination with CD1c⁺ myeloid dendritic cells (cDC2s), plasmacytoid dendritic cells (pDCs) or the combination. Immunological response was the primary endpoint and secondary endpoints included safety and survival. In 80% of the patients, antigen-specific CD8⁺ T cells were detected in skin test-derived T cells and in 55% of patients, antigen-specific CD8⁺ T cells were detectable in peripheral blood. Functional interferon-γ-producing T cells were found in the skin test of 64% of the patients. Production of nDC vaccines meeting release criteria was feasible for all patients. Vaccination only induced grade 1-2 adverse events, mainly consisting of fatigue. In conclusion, adjuvant dendritic cell vaccination with cDC2s and/or pDCs is feasible, safe and induced immunological responses in the majority of stage III melanoma patients.

SUBMITTER: Bloemendal M

PROVIDER: S-EPMC9746622 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Immunological responses to adjuvant vaccination with combined CD1c<sup>+</sup> myeloid and plasmacytoid dendritic cells in stage III melanoma patients.

Bloemendal Martine M Bol Kalijn F KF Boudewijns Steve S Gorris Mark A J MAJ de Wilt Johannes H W JHW Croockewit Sandra A J SAJ van Rossum Michelle M MM de Goede Anna L AL Petry Katja K Koornstra Rutger H T RHT Figdor Carl C Gerritsen Winald R WR Schreibelt Gerty G de Vries I Jolanda M IJM

Oncoimmunology 20211230 1

We evaluated the immunological responses of lymph-node involved (stage III) melanoma patients to adjuvant dendritic cell vaccination with subsets of naturally occurring dendritic cells (nDCs). Fifteen patients with completely resected stage III melanoma were randomized to receive adjuvant dendritic cell vaccination with CD1c<sup>+</sup> myeloid dendritic cells (cDC2s), plasmacytoid dendritic cells (pDCs) or the combination. Immunological response was the primary endpoint and secondary endpoints ...[more]

PMID: 36524210

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Project description:BackgroundPatients with advanced melanoma who progress after treatment with immune checkpoint-inhibitors (ICI) and BRAF-/MEK-inhibitors (if BRAF V600 mutated) have no remaining effective treatment options. The presence of CD1c (BDCA-1)+ and CD141 (BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment correlates with pre-existing immune recognition and responsiveness to immune checkpoint blockade. The synthetic saponin-based immune adjuvant AS01B enhances adaptive immunity through the involvement of myDC.MethodsIn this first-in-human phase I clinical trial, patients with metastatic melanoma refractory to ICI and BRAF-/MEK inhibitors (when indicated) were recruited. Patients received an intravenous administration of low-dose nivolumab (10 mg, every 2 weeks) plus an intratumoral (IT) administration of 10 mg ipilimumab and 50 µg (0.5 mL) AS01B (every 2 weeks). All myDC, isolated from blood, were injected on day 2 into the same metastatic lesion. Tumor biopsies and blood samples were collected at baseline and repeatedly on treatment. Multiplex immunohistochemistry (mIHC) was performed on biopsy sections to characterize and quantify the IT and peritumoral immune cell composition.ResultsStudy treatment was feasible and well tolerated without the occurrence of unexpected adverse events in all eight patients. Four patients (50%) obtained a complete response (CR) in the injected lesions. Of these, two patients obtained an overall CR, and one patient a partial response. All responses are ongoing after more than 1 year of follow-up. One additional patient had a stable disease as best response. The disease control rate was 50%. Median progression-free survival and overall survival were 24.1 and 41.9 weeks, respectively. Baseline tumor biopsies from patients who responded to treatment had features of T-cell exclusion. During treatment, there was an increased T-cell infiltration, with a reduced mean distance between T cells and tumor cells. Peripheral blood immune cell composition did not significantly change during study treatment.ConclusionsCombining an intratumoral injection of CD1c (BDCA-1)+ and CD141 (BDCA-3)+ myDC with repeated IT administration of ipilimumab and AS01B and systemic low-dose nivolumab is safe, feasible with promising early results, worthy of further clinical investigation.Trial registration numberClinicalTrials.gov identifier NCT03707808.

Dataset Information

Immunological responses to adjuvant vaccination with combined CD1c⁺ myeloid and plasmacytoid dendritic cells in stage III melanoma patients.

Publications

Immunological responses to adjuvant vaccination with combined CD1c<sup>+</sup> myeloid and plasmacytoid dendritic cells in stage III melanoma patients.

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Dataset Information

Immunological responses to adjuvant vaccination with combined CD1c+ myeloid and plasmacytoid dendritic cells in stage III melanoma patients.

Publications

Immunological responses to adjuvant vaccination with combined CD1c<sup>+</sup> myeloid and plasmacytoid dendritic cells in stage III melanoma patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Immunological responses to adjuvant vaccination with combined CD1c⁺ myeloid and plasmacytoid dendritic cells in stage III melanoma patients.