Migration Dynamics of Human NK Cell Preparations in Microchannels and Their Invasion Into Patient-Derived Tissue

Alina Moter1,2, Sonja Scharf3, Hendrik Schäfer3

  • 1Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt (Main), Germany.

Insights

Natural killer (NK) cells show greater invasion potential than T cells, even with similar speeds. This finding, using microfluidic technology, suggests NK cells are promising for cancer immunotherapy, especially engineered CAR-NK cells.

Area of Science:

  • Immunology
  • Cell Biology
  • Biotechnology

Background:

  • Natural killer (NK) cells possess inherent anti-cancer properties without prior antigen stimulation.
  • Chimeric antigen receptor (CAR) engineered NK cells show significant clinical potential for cancer therapy.
  • Limited NK cell migration and infiltration to tumor sites hinder their anti-tumor efficacy, due to poorly understood migration dynamics.

Purpose of the Study:

  • To investigate the intrinsic motility and invasion potential of NK cells.
  • To compare NK cell migration and invasion capabilities with T cells.
  • To assess the impact of tumor cells and genetic engineering (CARs) on NK cell behavior.

Main Methods:

  • Utilized innovative microfluidic microchannel technology to study NK cell motility.
  • Assessed baseline, activated, and proliferating NK cells against T cells.
  • Employed high-resolution 4D confocal imaging in patient-derived lymphatic tissues to evaluate invasion capacity.

Main Results:

  • NK cells demonstrated a greater invasion potential compared to T cells, despite comparable cell velocities.
  • NK cell nuclear flexibility may contribute to their enhanced invasion capabilities.
  • CD19-CAR-NK cell preparations exhibited similar motility to non-transduced NK cells in lymphoid tissue but showed improved targeted migration in tumor tissue.

Conclusions:

  • NK cells possess superior intrinsic invasion potential over T cells.
  • Genetic engineering with CARs does not impede NK cell motility and enhances tumor-specific migration.
  • NK cells, particularly CAR-NK cells, are suitable candidates for targeting difficult-to-reach tumors in immunotherapy.

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