Muramyl dipeptide CD10 monoclonal antibody immunoconjugates inhibited acute leukemia in nude mice

Biosci Rep. 2023 Apr 26;43(4):BSR20222668. doi: 10.1042/BSR20222668.

Abstract

Minimal residual disease (MRD) is one of the causes of leukemia recurrence. Previously, we developed anti-CD10 mAb conjugated to muramyl dipeptide immunoconjugate (MDP-Ab) for immune enhancement. The present study aimed to investigate anti-leukemia effect of MDP-Ab administered via different methods in leukemia ectopic graft nude mouse model. BALB/c nude mice were injected with Nalm-6 cells subcutaneously to establish leukemia xenografts in nude mice as a model. MDP-Ab or/and human lymphocytes (LYM) was injected into different sites of the nude mice. Immunohistochemistry staining of CDs in the bone marrow, liver and spleen was performed. IFN-γ was detected by ELISA. We detected the metastasis of leukemia cells to the liver, spleen and bone marrow in nude mouse leukemia model. MDP-Ab and LYM inhibited the growth of tumors, and simultaneous injection of MDP-Ab and LYM into the tumor inhibited the growth of tumors. IFN-γ levels in MDP-Ab (ca) + h-LYM (ca) group, MDP-Ab (ca) + h-LYM (ip) group, MDP-Ab (iv) + h-LYM (ip) group and PBS (ca) + h-LYM (ca) group were significantly higher than those in control group, while IFN-γ level in MDP-Ab (ca) + h-LYM (ca) group was the highest. Moreover, MDP-Ab and h-LYM promoted the expression of hCD4 and hCD8, with the highest expression in MDP-Ab (ca) + h-LYM (ca) group. In conclusion, MDP-Ab effectively promoted the production of IFN-γ, enhanced the antitumor immunity of T lymphocytes and inhibited leukemia.

Keywords: acute lymphoblastic leukemia; anti-CD10 mAb; immunotherapy; minimal residual disease; muramyl dipeptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
  • Animals
  • Antibodies, Monoclonal
  • Disease Models, Animal
  • Humans
  • Immunoconjugates*
  • Leukemia, Myeloid, Acute*
  • Mice
  • Mice, Nude

Substances

  • Acetylmuramyl-Alanyl-Isoglutamine
  • Antibodies, Monoclonal
  • Immunoconjugates