Effects of the combination of a monoclonal agonistic mouse anti-OX40 antibody and toll-like receptor agonists: Unmethylated CpG and LPS on an MB49 bladder cancer cell line in a mouse model

PLoS One. 2022 Jul 8;17(7):e0270802. doi: 10.1371/journal.pone.0270802. eCollection 2022.

Abstract

Purpose: The basis of the antitumor immunotherapy, of which the purpose is the stimulation of the immune system. We have used two of the Pathogen Associated Molecular Patterns: unmethylated CpG oligonucleotide, a ligand of Toll-like receptor 9 (TLR9), and lipopolysaccharide (LPS) which is recognized by TLR4, combined with an agonistic OX40 receptor-specific monoclonal antibody (anti-OX40), which is expressed by activated regulatory T-cells (and by other activated T-cell populations as well). The objective of this study was to prove the effectiveness of the aforementioned compounds in an animal model, on a bladder cancer cell line.

Methods: We have instilled MB49 cells subcutaneously, to the left musculus biceps femoris. We have created three observation groups, each containing ten mice. After eleven days, all treated mice bearing the size of 5-8 mm (in diameter) tumor were administered CpG + anti-OX40 or LPS + anti-OX40 three times with a three-day lap between each treatment. Mice in the control group did not receive any treatment.

Results: All the specimens from the control and LPS + anti-OX40 groups have died by the sixtieth day of the observation period, however, five mice from the CpG + anti-OX40 group were still alive. The experiment lasted until the last surviving mouse died, which occurred on the 357th day after tumor implantation.

Discussion: The treatment with LPS did not make anti-OX40 more potent and did not increase the survival times. However, CpG + anti-OX40 has shown increased antitumor activity compared to the other two groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Cell Line
  • Disease Models, Animal
  • Immunotherapy
  • Lipopolysaccharides* / pharmacology
  • Mice
  • Receptors, OX40
  • Toll-Like Receptor 9
  • Urinary Bladder Neoplasms* / drug therapy

Substances

  • Antibodies
  • Lipopolysaccharides
  • Receptors, OX40
  • Toll-Like Receptor 9

Grants and funding

This study was supported by the European Union, and co-financed by the European Social Fund in the form of a grant (EFOP-3.6.3-VEKOP-16-2017-00005, project title: Strengthening the scientific replacement by supporting the academic workshops and programs of students, developing a mentoring process) to DG. This study was also funded by the National Research, Development and Innovation Fund of Hungary under the Tématerületi Kiválósági Program 2020 funding scheme in the form of a grant (2020-4.1.1-TKP2020) to ML. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.