Biomedicines

1202 KiB

Open AccessArticle

Enzyme-Linked Immunosorbent Spot Assay for the Detection of Wilms’ Tumor 1-Specific T Cells Induced by Dendritic Cell Vaccination

by Yumiko Higuchi, Terutsugu Koya, Miki Yuzawa, Naoko Yamaoka, Yumiko Mizuno, Kiyoshi Yoshizawa, Koichi Hirabayashi, Takashi Kobayashi, Kenji Sano and Shigetaka Shimodaira

Biomedicines 2015, 3(4), 304-315; https://doi.org/10.3390/biomedicines3040304 - 4 Dec 2015

Cited by 11 | Viewed by 5280

Abstract

Background: Despite recent advances in cancer immunotherapy and the development of various assays for T cell assessment, a lack of universal standards within immune monitoring remains. The objective of this study was to evaluate the enzyme-linked immunosorbent spot (ELISpot) assay in comparison with major histocompatibility complex-tetramer analysis in the context of dendritic cell (DC)-based cancer immunotherapy. Methods: The ELISpot assay was performed on peripheral blood mononuclear cells to assess reproducibility, daily precision, and linearity using HLA-A*24:02-restricted Cytomegalovirus peptide. Wilms’ tumor 1 (WT1) antigen-specific cytotoxic T cells were then evaluated by both the ELISpot assay and WT1 tetramer analysis in peripheral blood from 46 cancer patients who received DC vaccinations pulsed with human leukocyte antigen (HLA)-A*24:02-restricted modified WT1 peptides. Results: The ELISpot assay was proven to have reproducibility (coefficient of variation (CV) ranged from 7.4% to 16.3%), daily precision (CV ranged from 5.0% to 17.3%), and linearity (r = 0.96–0.98). WT1-specific immune responses were detected by the ELISpot assay in 34 out of 46 patients (73.9%) post-vaccination. A Spearman’s rank-correlation coefficient of 0.82 between the ELISpot assay and WT1 tetramer analysis was obtained. Conclusion: This is the first report of a comparison of an ELISpot assay and tetramer analysis in the context of dendritic cell (DC)-based cancer immunotherapy. The ELISpot assay has reproducibility, linearity, and excellent correlation with the WT1 tetramer analysis. These findings suggest that the validated ELISpot assay is useful to monitor the acquired immunity by DC vaccination targeting WT1. Full article

(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)

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1303 KiB

Open AccessFeature PaperReview

Primary Human Blood Dendritic Cells for Cancer Immunotherapy—Tailoring the Immune Response by Dendritic Cell Maturation

by Simone P. Sittig, I. Jolanda M. De Vries and Gerty Schreibelt

Biomedicines 2015, 3(4), 282-303; https://doi.org/10.3390/biomedicines3040282 - 2 Dec 2015

Cited by 21 | Viewed by 9849

Abstract

Dendritic cell (DC)-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c⁺ and CD141⁺ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent in vivo functioning and mark them as promising tools for future vaccination strategies. Full article

(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)

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2488 KiB

Open AccessReview

Circulating MicroRNAs as Biomarkers and Mediators of Cell–Cell Communication in Cancer

by Molly A. Taylor

Biomedicines 2015, 3(4), 270-281; https://doi.org/10.3390/biomedicines3040270 - 9 Nov 2015

Cited by 11 | Viewed by 5672

Abstract

The realization of personalized medicine for cancer will rely not only on the development of new therapies, but on biomarkers that direct these therapies to the right patient. MicroRNA expression profiles in the primary tumor have been shown to differ between cancer patients and healthy individuals, suggesting they might make useful biomarkers. However, examination of microRNA expression in the primary tumor requires an invasive biopsy procedure. More recently, microRNAs have been shown to be released from the primary tumor into the circulation where they can be utilized as non-invasive biomarkers to diagnose patients, predict prognosis, or indicate therapeutic response. This review provides an overview of the current use of circulating microRNAs as biomarkers as well as recent findings on their role in regulating cell signaling interactions in the tumor microenvironment. Full article

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Biomedicines, Volume 3, Issue 4 (December 2015) – 3 articles , Pages 270-315

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