Development of minimally invasive cancer immunotherapy using anti-disialoganglioside GD2 antibody-producing mesenchymal stem cells for a neuroblastoma mouse model

Pediatr Surg Int. 2022 Dec 9;39(1):43. doi: 10.1007/s00383-022-05310-z.

Abstract

Purpose: Mouse IgG anti-disialoganglioside GD2 antibody-secreting mouse mesenchymal stem cells (anti-GD2-MSCs) were developed, and their anti-tumor effects were validated in an in vivo neuroblastoma mouse model.

Methods: Anti-GD2 antibody constructs were generated, incorporating FLAG-tagged single-chain fragment variables against GD2 fused to a linker sequence, and a fragment of a stationary portion was changed from human IgG to mouse IgG and GFP protein. The construct was lentivirally introduced into mouse MSCs. A syngeneic mouse model was established through the subcutaneous transplantation of a tumor tissue fragment from a TH-MYCN transgenic mouse, and the homing effects of anti-GD2-MSCs were validated by In vivo imaging system imaging. The syngeneic model was divided into three groups according to topical injection materials: anti-GD2-MSCs with IL-2, IL-2, and PBS. The tumors were removed, and natural killer (NK) cells were counted.

Results: Anti-GD2-MSCs showed homing effects in syngeneic models. The growth rate of subcutaneous tumors was significantly suppressed by anti-GD2-MSCs with IL-2 (p < 0.05). Subcutaneous tumor immunostaining showed an increased NK cell infiltration in the same group (p < 0.01).

Conclusion: Anti-GD2-MSCs using mouse IgG showed a homing effect and significant tumor growth suppression in syngeneic models. Anti-GD2-MSC-based cellular immunotherapy could be a novel therapeutic strategy for intractable neuroblastoma.

Keywords: Anti-GD2 antibody; Immunotherapy; Mesenchymal stem cell; Neuroblastoma.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gangliosides / therapeutic use
  • Humans
  • Immunoglobulin G / therapeutic use
  • Interleukin-2 / therapeutic use
  • Mesenchymal Stem Cells*
  • Mice
  • Mice, Transgenic
  • Neuroblastoma* / metabolism

Substances

  • Gangliosides
  • Interleukin-2
  • Immunoglobulin G