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Updated: Jul 16, 2026
Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
Published on: October 30, 2016
Interim report on engineered NK cell trial in lung cancer refractory to immune checkpoint inhibitors
Miguel A Villalona-Calero1, Lei Tian2, Xiaochen Li3
1The Department of Medical Oncology and Experimental Therapeutics, Beckman Research Institute and Comprehensive Cancer Center.
Background:
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality, necessitating the exploration of alternate therapeutic approaches. Tumor-reactive or activated-by-cytokine killers (TRACK) are PD-L1+, highly cytolytic NK cells derived from umbilical cord blood NK cells and engineered to express soluble IL-15 (sIL15), and these cells show promise in preclinical studies against NSCLC.
Methods:
We assessed safety, persistence, homing, and cytotoxic activity in 6 patients with advanced, refractory, and progressing NSCLC who received a low dose of unmatched, allogeneic, off-the-shelf sIL15_TRACK NK cells. We evaluated NK cell presence and persistence with droplet digital PCR (ddPCR), flow cytometry, and immunofluorescence staining.
Results:
sIL15_TRACK NK cells had peak measurements at 1 hour and became undetectable 4 hours after each infusion. Cognate ligands to activating NK cell receptors were found in NSCLC. sIL15_TRACK NK cells were observed in a lung tumor biopsy 7 days after the final infusion, confirming their sustainment and tumor-homing ability. They retained cytolytic function following isolation from the lung tumor. Three of 6 patients achieved disease stabilization on repeat imaging, while the others progressed.
Conclusion:
Unmatched, allogeneic, cryopreserved, off-the-shelf sIL15_TRACK NK cells express activating receptors, home to tumor sites that express their cognate ligands, and retain cytolytic activity after infusion, underscoring their potential as a therapeutic approach in solid tumors. At low doses, the therapy was safely administered and showed preliminary evidence of activity in 3 of 6 patients with advanced and progressive NSCLC. Additional dose escalation cohorts and coadministration with atezolizumab are planned.
Clinicaltrials:
gov NCT05334329.
Funding:
Funding was provided by CytoImmune Therapeutics and grants from the National Cancer Institute (CA266457, CA033572, and CA210087).
Insights
Engineered NK cells (sIL15_TRACK) show potential for treating non-small cell lung cancer. These cells homed to tumors and retained activity, with 3 of 6 patients achieving disease stabilization.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality.
- Novel therapeutic strategies are crucial for managing advanced NSCLC.
- Tumor-reactive or activated-by-cytokine killers (TRACK) are engineered NK cells showing preclinical promise.
Purpose of the Study:
- To assess the safety, persistence, homing, and cytotoxic activity of sIL15_TRACK NK cells in patients with advanced NSCLC.
- To evaluate the therapeutic potential of off-the-shelf, allogeneic NK cells in solid tumors.
Main Methods:
- A low dose of unmatched, allogeneic, off-the-shelf sIL15_TRACK NK cells was administered to 6 patients with advanced, refractory NSCLC.
- NK cell presence and persistence were evaluated using droplet digital PCR, flow cytometry, and immunofluorescence.
- Tumor biopsies were analyzed for NK cell infiltration and function.
Main Results:
- sIL15_TRACK NK cells peaked at 1 hour and were undetectable by 4 hours post-infusion.
- NK cells were detected in a lung tumor biopsy 7 days after the final infusion, demonstrating tumor homing and persistence.
- Three out of six patients achieved disease stabilization, while the remaining patients progressed.
Conclusions:
- Off-the-shelf sIL15_TRACK NK cells can home to tumors expressing cognate ligands and retain cytolytic activity.
- Low-dose administration was safe, with preliminary evidence of activity in advanced NSCLC.
- Further studies involving dose escalation and combination therapy are warranted.
