Humoral anti-KLH responses in cancer patients treated with dendritic cell-based immunotherapy are dictated by different vaccination parameters
Publication year
2012Source
Cancer Immunology Immunotherapy, 61, 11, (2012), pp. 2003-11ISSN
Publication type
Article / Letter to editor
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Organization
Medical Oncology
Tumorimmunology
Nuclear Medicine
Blood Transfusion and Transplantation Immunology
Paediatrics - OUD tm 2017
Laboratory of Medical Immunology
Journal title
Cancer Immunology Immunotherapy
Volume
vol. 61
Issue
iss. 11
Page start
p. 2003
Page end
p. 11
Subject
N4i 4: Auto-immunity, transplantation and immunotherapy; N4i 4: Auto-immunity, transplantation and immunotherapy NCMLS 2: Immune Regulation; NCMLS 2: Immune Regulation; NCMLS 2: Immune Regulation ONCOL 3: Translational research; ONCOL 2: Age-related aspects of cancer NCMLS 2: Immune Regulation; ONCOL 3: Translational research; ONCOL 3: Translational research NCMLS 2: Immune Regulation; Laboratory Medicine - Radboud University Medical Center; Medical Imaging - Radboud University Medical CenterAbstract
PURPOSE: Keyhole limpet hemocyanin (KLH) attracts biomedical interest because of its remarkable immunostimulatory properties. Currently, KLH is used as vaccine adjuvant, carrier protein for haptens and as local treatment for bladder cancer. Since a quantitative human anti-KLH assay is lacking, it has not been possible to monitor the dynamics of KLH-specific antibody (Ab) responses after in vivo KLH exposure. We designed a quantitative assay to measure KLH-specific Abs in humans and retrospectively studied the relation between vaccination parameters and the vaccine-induced anti-KLH Ab responses. EXPERIMENTAL DESIGN: Anti-KLH Abs were purified from pooled serum of melanoma patients who have responded to KLH as a vaccine adjuvant. Standard isotype-specific calibration curves were generated to measure KLH-specific Ab responses in individual serum samples using ELISA. RESULTS: KLH-specific IgM, IgA, IgG and all IgG-subclasses were accurately measured at concentrations as low as 20 mug/ml. The intra- and inter-assay coefficients of variation of this ELISA were below 6.7 and 9.9 %, respectively. Analyses of 128 patients demonstrated that mature DC induced higher levels of KLH-specific IgG compared to immature DC, prior infusion with anti-CD25 abolished IgG and IgM production and patients with locoregional disease developed more robust IgG responses than advanced metastatic melanoma patients. CONCLUSIONS: We present the first quantitative assay to measure KLH-specific Abs in human serum, which now enables monitoring both the dynamics and absolute concentrations of humoral immune responses in individuals exposed to KLH. This assay may provide a valuable biomarker for the immunogenicity and clinical effectiveness of KLH-containing vaccines and therapies.
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