Preparation and identification of a novel immunomodulator composed of muramyl dipeptide and anti-CD10 monoclonal antibody for treatment of minimal residual disease in acute leukemia children

Ling-zhen Wang; Li-rong Sun; Yan-xia Zhao; Ling-li Wang

doi:10.1016/j.intimp.2011.03.022

Preparation and identification of a novel immunomodulator composed of muramyl dipeptide and anti-CD10 monoclonal antibody for treatment of minimal residual disease in acute leukemia children

Int Immunopharmacol. 2011 Sep;11(9):1211-9. doi: 10.1016/j.intimp.2011.03.022. Epub 2011 Apr 12.

Authors

Ling-zhen Wang¹, Li-rong Sun, Yan-xia Zhao, Ling-li Wang

Affiliation

¹ The Affiliated Hospital of Medical College, Qingdao University, Shandong 266003, PR China. hopewang2006@hotmail.com

PMID: 21492747
DOI: 10.1016/j.intimp.2011.03.022

Abstract

Targeted therapy is a potentially useful approach for antileukemic therapy, in particular eliminating minimal residual disease (MRD) to prevent tumor relapse. In this study, the immunomodulator (MDP-Ab) was constructed by coupling anti-CD10 monoclonal antibody (MAb) and muramyl dipeptide (MDP) using heterobifunctional reagent SPDP and the activity of MDP-Ab through dendritic cells (DCs)-based immunotherapy was identified in targeted therapy for leukemia. Results showed that the molecular ratio of purified MDP-Ab immunomodulator was about 2:1 according to electrospray ionization mass spectrometry (ESI-MS). The immunoreactivity and specificity of the new immunomodulator on CD10 antigen was identical to that of unconjugated native anti-CD10 MAb. The immunomodulatory effect of MDP-Ab immunoconjugate on peripheral blood dendritic cells (PBDCs) from children with acute lymphoblastic leukemia (ALL) exhibited upregulated expression of HLA-DR, co-stimulatory marker (CD80 and CD86) and maturity marker (CD83), increased cytokine secretion (interleukin-12, IL-12) and enhanced autostimulatory activity. These results in vitro suggested that MDP-Ab immunoconjugate may be a suitable candidate for targeting trials and support the further development of vaccination with the new immunomodulator-triggered DCs as a post-remission treatment to prevent relapse in ALL children.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylmuramyl-Alanyl-Isoglutamine / chemistry*
Acetylmuramyl-Alanyl-Isoglutamine / immunology
Antibodies, Monoclonal / chemistry*
Antibodies, Monoclonal / immunology
Antigens, CD / immunology
Antigens, CD / metabolism
Child
Dendritic Cells / immunology
Dendritic Cells / metabolism
Dendritic Cells / pathology
Endocytosis / immunology
HL-60 Cells
HLA-DR Antigens / genetics
HLA-DR Antigens / immunology
HLA-DR Antigens / metabolism
Humans
Immunoconjugates / chemistry*
Immunoconjugates / immunology
Immunoconjugates / therapeutic use
Immunologic Factors / chemical synthesis*
Immunologic Factors / chemistry
Immunologic Factors / immunology
Immunologic Factors / therapeutic use
Immunophenotyping / methods
Immunotherapy / methods
Interleukin-12 / immunology
Interleukin-12 / metabolism
Neoplasm, Residual / immunology
Neoplasm, Residual / metabolism
Neoplasm, Residual / therapy
Neprilysin / immunology*
Neprilysin / metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
Succinimides / chemistry
T-Lymphocytes / immunology
T-Lymphocytes / metabolism
Tumor Cells, Cultured
Up-Regulation / immunology

Substances

Antibodies, Monoclonal
Antigens, CD
HLA-DR Antigens
Immunoconjugates
Immunologic Factors
Succinimides
Interleukin-12
N-succinimidyl 3-(2-pyridyldithio)propionate
Acetylmuramyl-Alanyl-Isoglutamine
Neprilysin