title: 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.
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.
authors.affiliation: The Affiliated Hospital of Medical College, Qingdao University, Shandong 266003, PR China. hopewang2006@hotmail.com
authors.forename: Ling-zhen
authors.initials: LZ
authors.lastname: Wang
authors.forename: Li-rong
authors.initials: LR
authors.lastname: Sun
authors.forename: Yan-xia
authors.initials: YX
authors.lastname: Zhao
authors.forename: Ling-li
authors.initials: LL
authors.lastname: Wang
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002648:Child; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004705:Endocytosis / Q000276:immunology; D018922:HL-60 Cells; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D016130:Immunophenotyping / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D018365:Neoplasm, Residual / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D015260:Neprilysin / Q000276:immunology* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D013388:Succinimides / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006684:HLA-DR Antigens; D018796:Immunoconjugates; D007155:Immunologic Factors; D013388:Succinimides; D018664:Interleukin-12; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D015260:Neprilysin