CD52 antigen expressed by malignant plasma cells can be targeted by alemtuzumab in vivo in NOD/SCID mice

Carmelo Carlo-Stella, Anna Guidetti, Massimo Di Nicola, Paolo Longoni, Loredana Cleris, Cristiana Lavazza, Marco Milanesi, Raffaella Milani, Matteo Carrabba, Lucia Farina, Franca Formelli, Alessandro M. Gianni, Paolo Corradini

Research output: Contribution to journalArticle

Abstract

Objective: To explore new treatments specifically targeting malignant plasma cells (PCs), we examined CD52 antigen expression on primary PCs as well as multiple myeloma (MM) cell lines, and investigated in vivo the antimyeloma activity of alemtuzumab. Materials and Methods: PCs were enriched from the marrow of MM patients (n = 39) according to CD138 expression and then analyzed by 3-color flow cytometry and quantitative PCR. The in vivo activity of alemtuzumab was evaluated in a xenotransplant model of MM in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Results: CD52 expression revealed a substantial heterogeneity in terms of both percentage of positive cells and fluorescence intensity, with 25/39 (64%) MM patients showing ≥30% CD138+ PCs expressing the CD52 antigen (mean = 79%; range, 33-100%). Similarly to primary cells, cell lines showed heterogeneous CD52 expression. Expression of CD52 mRNA by quantitative PCR analysis strongly correlated with CD52 antigen detection by flow cytometry. In vivo, alemtuzumab treatment significantly increased the median survival of animals with an early- (64 vs 77 days, p ≤ 0.0005) or advanced-stage (66 vs 75 days, p ≤ 0.02) disease. Conclusion: We conclude that: 1) CD52 is expressed on PCs of a significant proportion of MM patients; 2) alemtuzumab used as a single agent exerts a good antitumor activity in NOD/SCID mice bearing an early-stage disease; and 3) alemtuzumab might have therapeutic potential in a subset of MM patients.

Original languageEnglish
Pages (from-to)721-727
Number of pages7
JournalExperimental Hematology
Volume34
Issue number6
DOIs
Publication statusPublished - Jun 2006

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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