Dataset Information

NIMG-25. ADVANCED MRI ASSESSMENT DURING DENDRITIC CELL IMMUNOTHERAPY

ABSTRACT: Abstract BACKGROUND Evaluating changes induced by immunotherapies on conventional brain MRI can be difficult because those treatments may produce an inflammatory response. To explore the contribution of quantitative MRI biomarkers, we examined advanced MRI findings in first diagnosis glioblastoma (GBM) patients treated with dendritic cell (DC) immunotherapy added to standard treatment. METHODS A retrospective analysis was performed on longitudinal MRIs obtained by 22 patients enrolled in the EUDRACT N° 2008-005035-15 trial. The following parameters were collected: tumor volume (TV), mean normalized tumoral CBV (rCBV), Mean normalized tumoral ADC (rADC), semi-automatic ADC mean (ADCmean), ADC mode (ADCmode), ADC kurtosis (ADCkurt), ADC skewness (ADCskew). RESULTS Ten patients were defined, based on PFS >12 months, to have received benefit from the treatment (responder patients). After the first four vaccinations rADC significantly decreased in responders only (1.34 ± 0.17 vs 1.23 ±0.23 p=0.028). A decrease in rADC mean value ? 0.13 and a change in ADCskew ? -0.14 were significant predictors of longer PFS (17.2 vs 10.2 p=0.04; 15.4 vs 9.3 m p=0.02) and OS (33 vs 19.9 p=0.003; 29 vs 12.4 p=0.002). During the follow-up 18 patients experienced progression and 7 pseudoprogression according to RANO criteria. A significant increase of rCBV (4.25 to 5.38, p=0.04), and a significant decrease in rADCmean (1.17 vs 1.01) (p=0.004) were only observed in patients with true tumor progression. A ?rCBV value ? 2.07 was able to distinguish the two conditions with a sensitivity of 100% and specificity of 60% (p=0.004). CONCLUSION An early decrease in rADC and limited reduction of ADCskew are related to longer survival in GBM patients treated with DC immunotherapy, added to standard care, suggesting the relevance of hypercellularity in the first phase of the treatment. Modification of rCBV can be useful in distinguishing progression and pseudoprogression

SUBMITTER: Eoli M

PROVIDER: S-EPMC5692002 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Monocyte-derived dendritic cell (DC)-based vaccines loaded with tumor self-antigens represent a novel approach in anticancer therapy. We evaluated DC-based anticancer immunotherapy (ITx) in an academic Phase I/II clinical trial for children, adolescent, and young adults with progressive, recurrent, or primarily metastatic high-risk tumors. The primary endpoint was safety of intradermal administration of manufactured DCs. Here, we focused on relapsing high-risk sarcoma subgroup representing a major diagnosis in DC clinical trial. As a part of peripheral blood immunomonitoring, we evaluated quantitative association between basic cell-based immune parameters. Furthermore, we describe the pattern of these parameters and their time-dependent variations during the DC vaccination in the peripheral blood immunograms. The peripheral blood immunograms revealed distinct patterns in particular patients in the study group. As a functional testing, we evaluated immune response of patient T-cells to the tumor antigens presented by DCs in the autoMLR proliferation assay. This analysis was performed with T-cells obtained prior to DC ITx initiation and with T-cells collected after the fifth dose of DCs, demonstrating that the anticancer DC-based vaccine stimulates a preexisting immune response against self-tumor antigens. Finally, we present clinical and immunological findings in a Ewing's sarcoma patient with an interesting clinical course. Prior to DC therapy, we observed prevailing CD8+ T-cell stimulation and low immunosuppressive monocytic myeloid-derived suppressor cells (M-MDSC) and regulatory T-cells (Tregs). This patient was subsequently treated with 19 doses of DCs and experienced substantial regression of metastatic lesions after second disease relapse and was further rechallenged with DCs. In this patient, functional ex vivo testing of autologous T-cell activation by manufactured DC medicinal product during the course of DC ITx revealed that personalized anticancer DC-based vaccine stimulates a preexisting immune response against self-tumor antigens and that the T-cell reactivity persisted for the period without DC treatment and was further boosted by DC rechallenge. Trial Registration Number: EudraCT 2014-003388-39.

Project description:Acute and chronic myeloid leukemia (AML, CML) are hematologic malignancies arising from oncogene-transformed hematopoietic stem/progenitor cells known as leukemia stem cells (LSCs). LSCs are selectively resistant to various forms of therapy including irradiation or cytotoxic drugs. The introduction of tyrosine kinase inhibitors has dramatically improved disease outcome in patients with CML. For AML, however, prognosis is still quite dismal. Standard treatments have been established more than 20 years ago with only limited advances ever since. Durable remission is achieved in less than 30% of patients. Minimal residual disease (MRD), reflected by the persistence of LSCs below the detection limit by conventional methods, causes a high rate of disease relapses. Therefore, the ultimate goal in the treatment of myeloid leukemia must be the eradication of LSCs. Active immunotherapy, aiming at the generation of leukemia-specific cytotoxic T cells (CTLs), may represent a powerful approach to target LSCs in the MRD situation. To fully activate CTLs, leukemia antigens have to be successfully captured, processed, and presented by mature dendritic cells (DCs). Myeloid progenitors are a prominent source of DCs under homeostatic conditions, and it is now well established that LSCs and leukemic blasts can give rise to "malignant" DCs. These leukemia-derived DCs can express leukemia antigens and may either induce anti-leukemic T cell responses or favor tolerance to the leukemia, depending on co-stimulatory or -inhibitory molecules and cytokines. This review will concentrate on the role of DCs in myeloid leukemia immunotherapy with a special focus on their generation, application, and function and how they could be improved in order to generate highly effective and specific anti-leukemic CTL responses. In addition, we discuss how DC-based immunotherapy may be successfully integrated into current treatment strategies to promote remission and potentially cure myeloid leukemias.

Dataset Information

NIMG-25. ADVANCED MRI ASSESSMENT DURING DENDRITIC CELL IMMUNOTHERAPY

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets