Targeting CD38 with Monoclonal Antibodies Disrupts Key Survival Pathways in Paediatric Burkitt's Lymphoma Malignant B Cells

Overview

Journal Clin Transl Immunology

Specialty Allergy & Immunology

Date 2024 Oct 4

PMID 39364393

Authors

Kathrin Klasener

Nadja Herrmann

Liliana Haversen

Timothy Sundell

Martina Sundqvist

Christina Lundqvist

Paul T Manna

Charlotte A Jonsson

Marcella Visentini

Diana Ljung Sass

Sarah McGrath

Kristoffer Grimstad

Alaitz Aranburu

Karin Mellgren

Linda Fogelstrand

Huamei Forsman

Olov Ekwall

Jan Boren

Inger Gjertsson

Michael Reth

Inga-Lill Martensson

Alessandro Camponeschi

Affiliations

Soon will be listed here.

Abstract

Objectives: Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells.

Methods: analyses of patient samples, combined with experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3-kinase (PI3K) pathway.

Results: Isatuximab was found to be more effective than daratumumab in disrupting B-cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes.

Conclusion: The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.

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