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Discover how PEPperPRINT Peptide Microarray products have been used in different fields of research.

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Epitope mapping of humoral immunogenicity of orvacabtagene autoleucel shows an IgM response with minimal impact on CAR T cellular kinetics

Liu, Xianghong; Hu, Hongxiang; Dai, Yanshan; Pazos, Michael; Gokemeijer, Jochem; Ogasawara, Ken; Stoevesandt, Oda; Stadler, Volker; Mora, Johanna; Jawa, Vibha
Mol Ther Adv.
May 2026
10.1016/j.omta.2026.201763
Orvacabtagene autoleucel (orva-cel) is a fully human B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cell therapy evaluated in a phase 1/2 study in patients with relapsed or refractory multiple myeloma (RRMM). To assess treatment-related immunogenicity, anti-CAR therapeutic domain-specific antibodies (ATAs) were monitored in 157 treated patients. The ATAs were detected in 44.6% of patients over the course of study, with titers and incidence increasing over time. The goal of this study was to further characterize the observed immune response. The ATA status did not affect CAR T cell expansion or patient survival outcomes, though reduced persistence was observed in ATA-positive patients. Comprehensive immune profiling—including isotype analysis and B cell epitope mapping—identified five immunodominant consensus peptide sequences within the CAR domain. These epitopes were targeted by both Immunoglobulin G (IgG) and Immunoglobulin M (IgM) isotypes, with a persistent IgM response detected in most ATA-positive individuals. Despite the presence of ATAs, no adverse impact on cellular expansion was observed, potentially due to lymphodepletion and baseline immune suppression characteristic of B cell malignancies. These data suggest that the limited functional T- and B-cell capacity in RRMM may attenuate the clinical consequences of ATA development. The in vitro immunogenicity risk assessment and epitope mapping identified immunogenic hotspots within the CAR structure, which could have led to the high incidence of immune response observed in the patients. However, the analysis from this study points to a weak clinically non-relevant nature of the response that could be attributed to the patient’s immune status and diseased state.

High-throughput identification of immunoreactive peptides and corresponding proteins from Anaplasma platys and Ehrlichia canis using peptide microarray chips

Llanes, Alejandro; Madesh, Swetha; Brangulis, Kalvis; Rajeev, Sreekumari
Front Cell Infect Microbiol.
Jan 2025
10.3389/fcimb.2025.1671309
INTRODUCTION: Anaplasma platys and Ehrlichia canis are rickettsial pathogens infecting dogs, with a worldwide distribution. Both species are obligate intracellular pathogens and colonize bone marrow-derived cells, with coinfections frequently reported in dogs. Although E. canis immunodominant proteins have been thoroughly characterized, very few high-throughput studies have been conducted to identify immunogenic proteins from Anaplasma spp. In this study, we used a methodology based on peptide microarray chips to identify immunoreactive peptides, either shared or species-specific, in the complete theoretical proteomes of both pathogens. METHODS: B-cell epitopes were predicted in the corresponding proteins from both species and ranked for synthesis on the peptide microarrays. These microarrays were screened with serum samples from antibody-positive dogs, as well as negative control sera from unexposed dogs. Additionally, we assessed the feasibility of integrating evidence gathered at the level of individual peptides to identify potentially immunogenic proteins contributing to the patterns of immunoreactivity observed on microarrays. RESULTS: Screening of peptide microarrays resulted in complex antibody reactivity patterns against thousands of peptides. After discarding peptides with cross-reactivity to negative control sera, we identified over 1,200 immunoreactive peptides, including ~80 peptides shared between the two species with almost identical sequences. Despite screening linear peptides, we were able to identify proteins previously reported as immunodominant in E. canis, some of which contain predominantly conformational epitopes. DISCUSSION: Our results suggest that a high-throughput strategy based on peptide microarrays is an effective approach for the rapid identification of immunoreactive peptides and the underlying immunogenic proteins. This study provides a foundation for developing novel diagnostic tools and vaccine candidates against A. platys and E. canis, including potential combined or multivalent formulations targeting both pathogens.

Anti-brolucizumab immune response as one prerequisite for rare retinal vasculitis/retinal vascular occlusion adverse events

Karle, Anette C.; Wrobel, Matthias B.; Koepke, Stephan; Gutknecht, Michael; Gottlieb, Sascha; Christen, Brigitte; Rubic-Schneider, Tina; Pruimboom-Brees, Ingrid; Leber, Xavier Charles; Scharenberg, Meike; Maciejewski, Benjamin; Turner, Oliver; Saravanan, Chandra; Huet, Francois; Littlewood-Evans, Amanda; Clemens, Andreas; Grosskreutz, Cynthia L.; Kearns, Jeffrey D.; Mehan, Pawan; Schmouder, Robert L.; Sasseville, Vito; Brees, Dominique
Sci. Transl. Med..
Feb 2023
10.1126/scitranslmed.abq5241
In October 2019, Novartis launched brolucizumab, a single-chain variable fragment molecule targeting vascular endothelial growth factor A, for the treatment of neovascular age-related macular degeneration. In 2020, rare cases of retinal vasculitis and/or retinal vascular occlusion (RV/RO) were reported, often during the first few months after treatment initiation, consistent with a possible immunologic pathobiology. This finding was inconsistent with preclinical studies in cynomolgus monkeys that demonstrated no drug-related intraocular inflammation, or RV/RO, despite the presence of preexisting and treatment-emergent antidrug antibodies (ADAs) in some animals. In this study, the immune response against brolucizumab in humans was assessed using samples from clinical trials and clinical practice. In the brolucizumab-naïve population, anti-brolucizumab ADA responses were detected before any treatment, which was supported by the finding that healthy donors can harbor brolucizumab-specific B cells. This suggested prior exposure of the immune system to proteins with structural similarity. Experiments on samples showed that naïve and brolucizumab-treated ADA-positive patients developed a class-switched, high-affinity immune response, with several linear epitopes being recognized by ADAs. Only patients with RV/RO showed a meaningful T cell response upon recall with brolucizumab. Further studies in cynomolgus monkeys preimmunized against brolucizumab with adjuvant followed by intravitreal brolucizumab challenge demonstrated that high ADA titers were required to generate ocular inflammation and vasculitis/vascular thrombosis, comparable to RV/RO in humans. Immunogenicity therefore seems to be a prerequisite to develop RV/RO. However, because only 2.1% of patients with ADA develop RV/RO, additional factors must play a role in the development of RV/RO.

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