A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor–dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2

Greene, Julia M.; Schneble, Erika J; Jackson, Doreen O.; Hale, Diane F.; Vreeland, Timothy J.; Flores, Madeline; Martin, Jonathan; Herbert, Garth S.; Hardin, Mark O.; Yu, Xianzhong; Wagner, Thomas E.; Peoples, George E.

doi:10.1007/s00262-016-1809-6

Cited by 28 publications

(14 citation statements)

References 45 publications

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“…185,[220][221][222] Finally, a few studies preferred to use "unpulsed" autologous (matured ex vivo) DCs, administered in combination with cytokineinduced killer cells (CIKs), chemotherapy and/or radiotherapy. [223][224][225][226] Other approaches included the use of autologous dendritomas, 227 allogeneic peripheral blood mononuclear cells matured ex vivo into DCs, 228,229 or autologous unpulsed DCs combined with ACT. 230 Regarding the distribution across different cancer types ( Fig.…”

Section: Completed Clinical Trialsmentioning

confidence: 99%

“…230 Regarding the distribution across different cancer types ( Fig. 1), patients harboring melanoma were most commonly enrolled in these trials, 186,196,198,205,213,221,223,227,[231][232][233][234] followed by patients with prostate cancer, 206,208,212,215 glioma or glioblastoma (GBM), 185,197,202,219 hepatocellular carcinoma, 204,211,220 non-small cell lung carcinoma (NSCLC), 207,214,230 renal cell carcinoma (RCC), 201,203 esophageal carcinoma, 216,226 and pancreatic ductal adenocarcinoma, 209,217 among others. Of note, only two trials included a wide range of advanced solid tumors refractory to previous treatments.…”

Section: Completed Clinical Trialsmentioning

confidence: 99%

“…218,219 Most of these publications documented DC-based vaccines to elicit immune responses (generally in combination with standard-of-care therapies) achieving disease stabilization in most cases and partial or complete responses at a comparatively lower frequency. In several instances, DC-based vaccines have been administered in combination with conventional immunostimulatory agents including cytokines (e.g., IL-2, colony stimulating factor 2 (CSF2; also known as GM-CSF), IFN-a2B, IFNg or IFNb), 199,205,221,224,227 the tetanus toxoid, 185 or TLR agonists. 211 Interestingly, a few clinical studies also tested DCbased vaccines in combination with ACT and ICBs.…”

Section: Completed Clinical Trialsmentioning

confidence: 99%

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Trial watch: Dendritic cell-based anticancer immunotherapy

et al. 2017

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Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings. There is considerable clinical interest in combining DC-based anticancer vaccines with T cell-targeting immunotherapies. This reflects the established capacity of DC-based vaccines to generate a pool of TAA-specific effector T cells and facilitate their infiltration into the tumor bed. In this Trial Watch, we survey the latest trends in the preclinical and clinical development of DC-based anticancer therapeutics. We also highlight how the emergence of immune checkpoint blockers and adoptive T-cell transfer-based approaches has modified the clinical niche for DC-based vaccines within the wide cancer immunotherapy landscape.

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Section: Completed Clinical Trialsmentioning

confidence: 99%

Section: Completed Clinical Trialsmentioning

confidence: 99%

Section: Completed Clinical Trialsmentioning

confidence: 99%

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Trial watch: Dendritic cell-based anticancer immunotherapy

et al. 2017

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“…The morbidity of MM has increased gradually in recent years and shows a younger trend (1,2). It accounts for ~2% of malignancies in terms of morbidity and ranks the third of skin malignancies (6.8–20%); the disease can occur in any part of the skin, which is dominant by the sites that are vulnerable to friction in the four extremities, and its characteristics are early metastasis, strong invasiveness and poor prognosis (3).…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNA-194 regulates human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway

et al. 2017

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In the present study, we analyzed the role of microRNA-194 circulating regulated human melanoma cell growth. We found that microRNA-194 expression was markedly suppressed in human melanoma patients, compared with negative control group. Next, disease-free survival (DFS) and overall survival (OS) of high expression in human melanoma patients was higher than those of low expression in human melanoma patients. MicroRNA-194 overexpression inhibited cell proliferation, induced apoptosis, increased caspase-3/−9 activities and promoted Bax/Bcl-2 of human melanoma cells. Furthermore, microRNA-194 overexpression also suppressed PI3K/AKT/FoxO3a signaling pathway and induced p53/p21 signaling pathway. PI3K inhibitor, suppressed PI3K, phosphorylation-AKT, FoxO3a protein expression and increased the effects of microRNA-194 overexpression on cell growth, apoptosis, caspase-3/−9 activities and Bax/Bcl-2 protein expression of human melanoma cells through the induction of p53/p21 signaling pathway. Taken together, these data indicate that circulating microRNA-194 regulated human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway.

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“…Further studies will be needed to evaluate the safety of the vaccines, even though studies with similar treatment report them as safe . An extended modelling framework with NAC and DC vaccination toxicity integrated with the current work will be helpful to completely understand the impact of this therapy on the patients.…”

Section: Discussionmentioning

confidence: 99%

Assessing the impact of the addition of dendritic cell vaccination to neoadjuvant chemotherapy in breast cancer patients: A model‐based characterization approach

Solans

Cerio

Elizalde

et al. 2019

Brit J Clinical Pharma

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Aims: Immunotherapy is a rising alternative to traditional treatment in breast cancer (BC) patients in order to transform cold into hot immune enriched tumours and improve responses and outcome. A computational modelling approach was applied to quantify modulation effects of immunotherapy and chemotherapy response on tumour shrinkage and progression-free survival (PFS) in naïve BC patients.Methods: Eighty-three Her2-negative BC patients were recruited for neoadjuvant chemotherapy with or without immunotherapy based on dendritic cell vaccination.Sequential tumour size measurements were modelled using nonlinear mixed effects modelling and linked to PFS. Data from another set of patients (n = 111) were used to validate the model.Results: Tumour size profiles over time were linked to biomarker dynamics and PFS. The immunotherapy effect was related to tumour shrinkage (P < .05), with the shrinkage 17% (95% confidence interval: 2-23%) being higher in vaccinated patients, confirmed by the finding that pathological complete response rates in the breast were higher in the vaccinated compared to the control group (25.6% vs 13.6%; P = .04). The whole tumour shrinkage time profile was the major prognostic factor associated to PFS (P < .05), and therefore, immunotherapy influences indirectly on PFS, showing a trend in decreasing the probability of progression with increased vaccine effects.Tumour subtype was also associated with PFS (P < .05), showing that luminal A BC patients have better prognosis.Conclusions: Dendritic cell-based immunotherapy is effective in decreasing tumour size. The semi-mechanistic validated model presented allows the quantification of the immunotherapy treatment effects on tumour shrinkage and establishes the relationship between the dynamics of tumour size and PFS.

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A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor–dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2

Cited by 28 publications

References 45 publications

Trial watch: Dendritic cell-based anticancer immunotherapy

Trial watch: Dendritic cell-based anticancer immunotherapy

Circulating microRNA-194 regulates human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway

Assessing the impact of the addition of dendritic cell vaccination to neoadjuvant chemotherapy in breast cancer patients: A model‐based characterization approach

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