Related Experiment Video
Updated: May 8, 2026
Quantifying Leukocyte Egress via Lymphatic Vessels from Murine Skin and Tumors
Published on: January 7, 2019
Quantitative assessment of extravasation of IL-15-secreting MSLN-CAR-NK-92 cells using tumor transparency imaging
Sera Hong1, Dohyeon Moon1, Seoin Hwang2
1College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
Background:
The extravasation of anticancer immune cells is a very important issue that must be understood to improve the anticancer effect of chimeric antigen receptor (CAR)-expressing anticancer immune cell therapy. To date, no study has been reported to quantitatively evaluate the degree of extravasation of anticancer immune cells escaping from tumor blood vessels to the tumor microenvironment (TME) at the microscopic level.
Methods:
In this study, for the first time, using tumor transparency imaging, the extent of extravasation of CAR-NK and NK cells in pancreatic tumors was determined. we used tumor transparency imaging, which preserves intact vasculature, to accurately measure the extravasation and infiltration of established MSLN-CAR-NK-92 cells and unmodified NK-92 cells in an NSG mouse model of pancreatic cancer. Extravasation was quantified by calculating the volume ratio of cells located inside versus outside tumor vessels.
Results:
Following intravenous infusion, MSLN-CAR-NK-92 cells showed higher extravasation rates (85.3% vs. 57.4%), penetration depths (185 μm vs. 128 μm), and average extravasated cell counts (7,717 vs. 2,311) compared with NK-92 cells. Further measures of penetration and cytotoxicity also favored MSLN-CAR-NK-92 cells, with CPA50/CPD50 values of 6,887 cells at 88 μm versus 3,509 cells at 45 μm, and CDA50/CDD50 values of 6,350 cells at 102 μm versus 2,023 cells at 48 μm, respectively. These findings highlight the value of extravasation efficiency as a metric for assessing immune cell performance in solid tumors.
Conclusion:
Considering these results, the extravasation efficiency of anticancer immune cells can be regarded as a valuable indicator for evaluating the effectiveness of CAR constructs designed for NK cells target pancreatic cancer. In this study, we establish a quantitative extravasation imaging platform for evaluating CAR-NK cell trafficking in pancreatic and cholangiocarcinoma tumor models. This approach provides a structured framework for assessing immune cell delivery and therapeutic distribution within the tumor microenvironment.
Insights
Chimeric antigen receptor (CAR)-NK cells show superior extravasation into pancreatic tumors compared to standard NK cells. This improved cell trafficking is a key indicator for enhancing CAR therapy effectiveness against solid tumors.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Extravasation of anticancer immune cells is critical for CAR therapy efficacy.
- Quantitative microscopic evaluation of immune cell extravasation into tumors is lacking.
- Understanding immune cell trafficking is vital for improving cancer treatment outcomes.
Purpose of the Study:
- To quantitatively evaluate the extravasation of CAR-NK cells versus NK cells in pancreatic tumors.
- To establish a novel imaging platform for assessing immune cell extravasation and infiltration.
- To determine the impact of CAR modification on immune cell delivery within the tumor microenvironment.
Main Methods:
- Utilized tumor transparency imaging to preserve intact vasculature for microscopic analysis.
- Quantified extravasation by measuring the volume ratio of cells inside versus outside tumor vessels.
- Assessed CAR-NK-92 and NK-92 cell extravasation and infiltration in an NSG mouse model of pancreatic cancer.
Main Results:
- MSLN-CAR-NK-92 cells demonstrated significantly higher extravasation rates (85.3% vs. 57.4%) compared to NK-92 cells.
- CAR-NK cells exhibited greater penetration depth and higher counts of extravasated cells within the tumor.
- Enhanced cytotoxicity and penetration were observed for CAR-NK-92 cells, indicating superior anti-tumor potential.
Conclusions:
- Extravasation efficiency is a valuable metric for evaluating CAR construct effectiveness in NK cell-based cancer therapy.
- The developed quantitative imaging platform provides a structured framework for assessing immune cell delivery in pancreatic and cholangiocarcinoma models.
- This approach aids in optimizing therapeutic distribution and improving CAR-NK cell performance in solid tumors.
More Related Videos
09:42Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis
Published on: June 26, 2019
05:08In vivo Imaging of Tumor Angiogenesis using Fluorescence Confocal Videomicroscopy
Published on: September 11, 2013