Natural dendritic cell vaccinations generate immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer

Creemers, Jeroen H A; Westdorp, Harm; Oort, Inge M. van; Schreibelt, Gerty; Gorris, Mark A.J.; Mehra, Niven; Simons, Michiel; Goede, Anna de; Rossum, M. van; Croockewit, Sandra; Figdor, Carl G.; Witjes, J. Alfred; Aarntzen, Erik H.J.G.; Mus, Roel; Gotthardt, Martin; Barentsz, Jelle O.; Vries, Jolanda De; Gerritsen, Winald R.

doi:10.1093/annonc/mdz253.005

Cited by 4 publications

(1 citation statement)

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“…Mean rPFS was 6.1 months. Results published in ESMO 2019 congress reported that patients who had non-progressive disease had more antigen-specific T cells (IFNγ+) compared to progressed patients ( 62 ). rPFS was 18.8 months in patients with high IFNγ+ cells and 5.1 months in patients with low IFNγ+ cells, indicating that immune activation as seen by an elevated amount of IFNγ+ cells would mediate prolonged rPFS in patients.…”

Section: Immuno-oncology Drug Development For Bone Metastasismentioning

confidence: 99%

Insights into immuno-oncology drug development landscape with focus on bone metastasis

Kähkönen,

Halleen,

MacRitchie

et al. 2023

Front. Immunol.

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Bone is among the main sites of metastasis in breast, prostate and other major cancers. Bone metastases remain incurable causing high mortality, severe skeletal-related effects and decreased quality of life. Despite the success of immunotherapies in oncology, no immunotherapies are approved for bone metastasis and no clear benefit has been observed with approved immunotherapies in treatment of bone metastatic disease. Therefore, it is crucial to consider unique features of tumor microenvironment in bone metastasis when developing novel therapies. The vicious cycle of bone metastasis, referring to crosstalk between tumor and bone cells that enables the tumor cells to grow in the bone microenvironment, is a well-established concept. Very recently, a novel osteoimmuno-oncology (OIO) concept was introduced to the scientific community. OIO emphasizes the significance of interactions between tumor, immune and bone cells in promoting tumor growth in bone metastasis, and it can be used to reveal the most promising targets for bone metastasis. In order to provide an insight into the current immuno-oncology drug development landscape, we used 1stOncology database, a cancer drug development resource to identify novel immunotherapies in preclinical or clinical development for breast and prostate cancer bone metastasis. Based on the database search, 24 immunotherapies were identified in preclinical or clinical development that included evaluation of effects on bone metastasis. This review provides an insight to novel immuno-oncology drug development in the context of bone metastasis. Bone metastases can be approached using different modalities, and tumor microenvironment in bone provides many potential targets for bone metastasis. Noting current increasing interest in the field of OIO, more therapeutic opportunities that primarily target bone metastasis are expected in the future.

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Section: Immuno-oncology Drug Development For Bone Metastasismentioning

confidence: 99%

Insights into immuno-oncology drug development landscape with focus on bone metastasis

Kähkönen,

Halleen,

MacRitchie

et al. 2023

Front. Immunol.

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Hormone Therapy Models

Padmanabhan

Meskin

Moustafa

2020

Series in BioEngineering

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Adjuvant Wilms’ tumour 1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high-grade glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase I/II clinical trial in Belgium

Van Genechten,

De Laere,

Van den Bossche

et al. 2024

BMJ Open

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Introduction Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms’ tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety ofWT1mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG. Methods and analysis 10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m2daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8–10×106cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150–200 mg/m2on days 1–5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life. Ethics and dissemination The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences. Trial registration number NCT04911621

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Natural dendritic cell vaccinations generate immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer

Cited by 4 publications

References 0 publications

Insights into immuno-oncology drug development landscape with focus on bone metastasis

Insights into immuno-oncology drug development landscape with focus on bone metastasis

Hormone Therapy Models

Adjuvant Wilms’ tumour 1-specific dendritic cell immunotherapy complementing conventional therapy for paediatric patients with high-grade glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase I/II clinical trial in Belgium

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