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Leukemia. 2018 Jun 28. doi: 10.1038/s41375-018-0182-1. [Epub ahead of print]

LRPAP1 is a frequent proliferation-inducing antigen of BCRs of mantle cell lymphomas and can be used for specific therapeutic targeting.

Author information

1
José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany. lorenz.thurner@uks.eu.
2
Dr. Senckenberg Institute of Pathology, Goethe University Hospital, Frankfurt am Main, Germany.
3
José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany.
4
Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany.
5
Second Department of Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
6
Saarland University Medical School, Institute of Pathology, Homburg/Saar, Germany.
7
Lymphoma Program, Abramson Cancer Center University of Pennsylvania, Philadelphia, PA, USA.

Abstract

The predominant usage of VH4-34 and V3-21 and reports of stereotyped CDR3s suggest a shared antigenic target of B-cell receptors (BCR) from mantle cell lymphomas (MCL). To identify the target antigens of MCL-BCRs, BCRs from 21 patients and seven MCL cell lines were recombinantly expressed and used for antigen screening. The BCRs from 8/21 patients and 2/7 MCL cell lines reacted specifically with the autoantigen low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1). High-titered and light chain-restricted anti-LRPAP1 serum antibodies were found in MCL patients, but not in controls. LRPAP1 induced proliferation by BCR pathway activation, while an LRPAP1-ETA' toxin-conjugate specifically killed MCL cells with LRPAP1-specific BCRs. Our results suggest a role of LRPAP1 in lymphomagenesis and maintenance of a considerable proportion of MCL cases by chronic autoantigenic stimulation, likely evolving from a chronic autoreactive B-cell response. Importantly, LRPAP1 can be used for a novel therapeutic approach that targets MCL with LRPAP1-reactive BCRs with high specificity.

PMID:
29955130
DOI:
10.1038/s41375-018-0182-1

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