Antibody immunotherapy targeting a novel B-cell lymphoma secreted biomarker

Abstract

Abstract We have used a patented (US 8,745,713) in vitro antibody platform technology to isolate fully human antibodies against a novel B cell lymphoma secreted biomarker, which is an isoform of the Fc Receptor-Like (FCRL) protein family. The FCRL isoform appears to inhibit CD4+ T cell recognition, and consequently would obstruct T cell immunosurveillance of B cell lymphoma. Targeted antibody immunotherapy is now a first-line treatment of B cell lymphoma due to the success of rituximab, a chimeric antibody that binds to and eliminates cells expressing the pan-B cell marker CD20. We envision that antibody targeting the secreted FCRL isoform would have a completely different mechanism of action from antibodies that bind to and eliminate cells expressing tumor antigens. Instead, anti-FCRL would be more analogous to antibodies that target immunoinhibitory molecules like CTLA4, or PD1 and its ligand PD-L1. Antibodies blocking these inhibitory interactions restore T cell function, ostensibly by promoting T cell priming in the case of CTLA4 blockade, and by preventing T cell exhaustion during PD1/PD-L1 blockade. Antibody targeting the FCRL lymphoma biomarker is instead expected to boost CD4+ T cell antigen presentation by DC and other professional APC, allowing for more robust T-cell anti-tumor responses. Furthermore, targeting the secreted FCRL isoform is not expected to have serious side effects like tumor lysis syndrome, nor affect the patients’ normal B cells. Moreover, since the FCRL biomarker was identified in serum of lymphoma patients, a clinical diagnostic screening assay could readily be developed to monitor for tumor progression and treatment response, as well as, identify candidate patients for FCRL targeted antibody immunotherapy.