CD54 is a surrogate marker of antigen presenting cell activation

There is no single universally accepted hallmark of antigen presenting cell (APC) activation. Instead a variety of methods are used to identify APCs and assess their activation state. These activation measures include phenotypic methods [e.g., assessing the increased expression of surface markers su...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2008-09, Vol.57 (9), p.1381-1390
Main Authors: Sheikh, N. A., Jones, L. A.
Format: Article
Language:English
Subjects:
Antigen Presentation
Antineoplastic agents
Biological activity
Biological and medical sciences
Biomarkers, Tumor - metabolism
Cancer
Cancer Research
Cells
Gene Expression Regulation, Neoplastic
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Humans
Immunology
Immunotherapy
Immunotherapy - methods
Intercellular Adhesion Molecule-1 - biosynthesis
Leukocytes, Mononuclear - cytology
Ligands
Lymphocytes
Lymphocytes - cytology
Medical sciences
Medicine
Medicine & Public Health
Oncology
Original
Original Article
Pharmacology. Drug treatments
Phenotype
Proteins
Recombinant Fusion Proteins - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tissue Extracts - pharmacology
Up-Regulation
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Summary:There is no single universally accepted hallmark of antigen presenting cell (APC) activation. Instead a variety of methods are used to identify APCs and assess their activation state. These activation measures include phenotypic methods [e.g., assessing the increased expression of surface markers such as major histocompatability (MHC) class II] and functional assays (e.g., evaluating the enhanced ability to take up and process antigen, or stimulate naïve T cells). Sipuleucel-T is an investigational autologous active cellular immunotherapy product designed to stimulate a T cell immune response against human prostatic acid phosphatase (PAP), an antigen highly expressed in prostate tissue. Sipuleucel-T consists of peripheral blood mononuclear cells (PBMCs), including activated APCs displaying epitopes of PAP. In order to develop a robust reproducible potency assay that is not hampered by MHC restriction we have developed a method to simply assess the biological activation of antigen presenting cells (APCs). In the course of sipuleucel-T characterization, we analyzed various phenotypic and functional parameters to define the activation state of APCs obtained from peripheral blood. Flow cytometric assays revealed that CD54+ cells are responsible for antigen uptake, and that expression of CD54 predominantly localizes to APCs. Costimulation, as measured by an allogeneic mixed lymphocytic reaction (alloMLR) assay, showed that activity was restricted to the CD54+ cell population. Similarly, CD54+ cells harbor all of the PAP-specific antigen presentation activity, as assayed using a PAP-specific HLA-DRβ1-restricted T cell hybridoma. Finally we show that CD54 expression is substantially and consistently upregulated on APCs during culture with a GM-CSF fusion protein, and that this upregulation activity can be quantified. Thus these data support the use of CD54 upregulation as a surrogate for assessing human APC activation and validates its utility as a potency measure of sipuleucel-T.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-008-0474-9