22 research outputs found
Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting
Cell-based therapy exploits modified human cells to treat diseases but its targeted application
in specific tissues, particularly those lying deep in the body where direct injection is not
possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to
direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour
sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic
iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the
tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into
tumours, resulting in increased tumour macrophage infiltration and reduction in tumour
burden and metastasis. Our study indicates that clinical MRI scanners can not only track the
location of magnetically labelled cells but also have the potential to steer them into one or
more target tissues
Natural Splice Variant of MHC Class I Cytoplasmic Tail Enhances Dendritic Cell-Induced CD8+ T-Cell Responses and Boosts Anti-Tumor Immunity
Dendritic cell (DC)-mediated presentation of MHC class I (MHC-I)/peptide complexes is a crucial first step in the priming of CTL responses, and the cytoplasmic tail of MHC-I plays an important role in modulating this process. Several species express a splice variant of the MHC-I tail that deletes exon 7-encoding amino acids (Δ7), including a conserved serine phosphorylation site. Previously, it has been shown that Δ7 MHC-I molecules demonstrate extended DC surface half-lives, and that mice expressing Δ7-Kb generate significantly augmented CTL responses to viral challenge. Herein, we show that Δ7-Db-expressing DCs stimulated significantly more proliferation and much higher cytokine secretion by melanoma antigen-specific (Pmel-1) T cells. Moreover, in combination with adoptive Pmel-1 T-cell transfer, Δ7-Db DCs were superior to WT-Db DCs at stimulating anti-tumor responses against established B16 melanoma tumors, significantly extending mouse survival. Human DCs engineered to express Δ7-HLA-A*0201 showed similarly enhanced CTL stimulatory capacity. Further studies demonstrated impaired lateral membrane movement and clustering of human Δ7-MHC-I/peptide complexes, resulting in significantly increased bioavailability of MHC-I/peptide complexes for specific CD8+ T cells. Collectively, these data suggest that targeting exon 7-encoded MHC-I cytoplasmic determinants in DC vaccines has the potential to increase CD8+ T-cell stimulatory capacity and substantially improve their clinical efficacy
Controlled-rate freezer cryopreservation of highly concentrated peripheral blood mononuclear cells results in higher cell yields and superior autologous T-cell stimulation for dendritic cell-based immunotherapy
Dendritic Cell Based Tumor Vaccination in Prostate and Renal Cell Cancer: A Systematic Review and Meta-Analysis
BACKGROUND: More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17) and RCC (12). Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD) amounted to a clinical benefit rate (CBR) of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403) revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1) and in RCC (OR 8.4, 95% CI 1.3-53.0). Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC) as well as access to draining lymph nodes on clinical outcome could be demonstrated. CONCLUSIONS/SIGNIFICANCE: As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines
Feasibility study of DCs/CIKs combined with thoracic radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer
Dendritic Cells Transfected with mRNA for p53, Survivin and hTERT as Treatment for Patients With Malignant Melanoma or Breast Cancer-A Phase I Study
Combined treatment with dendritic cell vaccine and low-dose cyclophosphamide in patients with malignant melanoma.
Combined Treatment with Dendritic Cell Vaccine and Low-Dose Cyclophosphamide in Patients with Malignant Melanoma
Melanoma patients treated with dendritic cell vaccination, interleukin-2, and metronomic cyclophosphamide: Results from a phase II trial.
Effects of a 12-Week Multimodal Exercise Intervention Among Older Patients with Advanced Cancer:Results from a Randomized Controlled Trial
BACKGROUND: Older patients with cancer are at risk of physical decline and impaired quality of life during oncological treatment. Exercise training has the potential to reduce these challenges. The study aim was to investigate the feasibility and effect of a multimodal exercise intervention in older patients with advanced cancer (stages III/IV). PATIENTS AND METHODS: Eighty-four older adults (≥65 years) with advanced pancreatic, biliary tract, or non-small cell lung cancer who received systemic oncological treatment were randomized 1:1 to an intervention group or a control group. The intervention was a 12-week multimodal exercise-based program including supervised exercise twice weekly followed by a protein supplement, a home-based walking program, and nurse-led support and counseling. The primary endpoint was change in physical function (30-second chair stand test) at 13 weeks. RESULTS: Median age of the participants was 72 years (interquartile range [IQR] 68-75). Median adherence to the exercise sessions was 69% (IQR 21-88) and 75% (IQR 33-100) for the walking program. At 13 weeks, there was a significant difference in change scores of 2.4 repetitions in the chair stand test, favoring the intervention group (p < .0001). Furthermore, significant beneficial effects were seen for physical endurance (6-minute walk test), hand grip strength, physical activity, symptom burden, symptoms of depression and anxiety, global health status (quality of life), and lean body mass. No effects were seen for dose intensity, hospitalizations, or survival. CONCLUSION: A 12-week multimodal exercise intervention with targeted support proved effective in improving physical function in older patients with advanced cancer during oncological treatment