Applying MAPPs Assays to Assess Drug Immunogenicity.
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ABSTRACT:
SUBMITTER: Karle AC
PROVIDER: S-EPMC7186346 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Applying MAPPs Assays to Assess Drug Immunogenicity.
Frontiers in immunology 20200421
Immunogenicity against biotherapeutic proteins (BPs) and the potential outcome for the patient are difficult to predict. <i>In vitro</i> assays that can help to assess the immunogenic potential of BPs are not yet used routinely during drug development. MAPPs (MHC-associated peptide proteomics) is one of the assays best characterized regarding its value for immunogenicity potential assessment. This review is focusing on recent studies that have employed human HLA class II-MAPPs assays to rank bio ...[more]
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Project description:The appended raw files, csv files and other documents were deposited in the public domain in support for the publication
Enabling Routine MHC-II Associated Peptide ProteomicS (MAPPs) for Risk Assessment of Drug-Induced Immunogenicity
Guido Steiner, Celine Marban-Doran, Jessica Langer, Tatiana Pimenova, Gonzalo Duran-Pacheco; Denise Sauter; Anja Langenkamp, Corinne Solier, Thomas Singer, Katharine Bray-French, and Axel Ducret
The abstract is appended below:
MHC-II Associated Peptide ProteomicS (MAPPs) is a mass spectrometry-based approach to identify and relatively quantitate naturally processed and presented MHC-II associated peptides that can potentially activate T cells and contribute to the immunogenicity of a drug. Acceptance of the MAPPs technology as an appropriate pre-clinical (and potentially clinical) immunogenicity risk assessment tool depends on its technical stability and robustness but also on the ability to compare results across experiments and donors. To this end, we developed a specialized MAPPs data processing pipeline, dataMAPPs, which presents complex mass spectrometric datasets in the form of heat maps (heatMAPPs) enabling rapid and convenient comparison between conditions and donors. A customized normalization procedure based on identified endogenous peptides standardizes signal intensities within and between donors and enable cross-experimental comparison. We evaluated the technical reproducibility of the MAPPs platform using tool compounds with respect to the most prominent experimental factors and found that the systematic biological differences across donors by far outweighed any technical source of variation. We illustrate the capability of the MAPPs platform to generate data that may be used for pre-clinical risk assessment of drug-induced immunogenicity and discuss its applicability in the clinics.
The raw files and associated data for publicly available compounds are appended in the depository. The database (dataMAPPS publication db.FASTA) that was used to search the raw files is also included.
The current dataset is divided in three sections, each with explaining documentation:
Folder Fig. 2_4_5 contains the raw files, the PEAKS identification files and the quantification files that were used to generate the Fig. 2, 4 and 5 of the publication. The raw files were also used to generate the test files deposited on http://SourceForge.net/projects/datamapps/ which is alsothe source to download the R source code for dataMAPPs.
Folder Fig. 6BC contains the raw files, the PEAKS identification files and the quantification files that were used to generate the Fig. 6 BC. The raw files used to generate Fig. 6A were not included; they have been generated using a compound that is proprietary.
Folder Fig. 8_KLH contains the raw files, the PEAKS identification files and the quantification files that were used to generate the Fig. 8.
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