Hepatocellular Carcinoma Therapeutic Response to Systemic Delivery of Engineered Natural Killer Cells in Combination Therapy with Sorafenib

Monday, March 31, 2025

3:18 PM – 3:27 PM CT

Location: Music City Center, 209 ABC

Presenting Author(s)

Luke Limfueco (he/him/his)

Medical Student
Western University of Health Sciences - College of Osteopathic Medicine of the Pacific, United States

Author/Co-author(s)

AE

Aydin Eresen, PhD (he/him/his)

Assistant Researcher
University of California, Irvine, United States
Zigeng Zhang, MD

Postdoctoral Fellow
University of California, Irvine, United States
Guangbo Yu, MS

PhD Student
University of California, Irvine, United States
QH

Qiaoming Hou, n/a

Lab Manager
University of California, Irvine, United States
ZZ

Zhuoli Zhang, MD, PhD

Principle Investigator
University of California Irvine, Department of Radiological Sciences, United States

Purpose: Cancer treatment outcomes are traditionally determined by monitoring changes in the longest tumor diameter, which is inadequate for assessing a tumor’s volumetric change and insufficient for evaluating response to immunotherapies. Herein, we use tumor volume change (ΔTV) to assess the therapeutic response of systemic delivery of engineered Natural Killer (eNK) cells with Sorafenib in rats with hepatocellular carcinoma (HCC).

Materials and Methods:

eNK cells were engineered by preactivating rat NK cells with IL-12/18 cytokines. 24 buffalo rats implanted with McA-RH7777 tumors were randomized to either eNK cell with Sorafenib, eNK cell alone, Sorafenib alone, or control. One week following implantation, an MRI scan was performed, and treatment was initiated. eNK cell delivery was achieved by systemic delivery using tail vein injection. Sorafenib was administered orally.

Multi-parametric MRI scans were repeated weekly for up to 4 weeks. The resulting images were uploaded to 3D Slicer, where tumors were meticulously traced slice-by-slice to calculate tumor volume. ΔTV was calculated for 1 week, 2 weeks, and 3 weeks after starting treatment and was compared between groups.

Results:

The ΔTV in the combination group was significantly lower compared to both the eNK cell and Sorafenib monotherapies. Compared to eNK cell alone, the combination group exhibited a lower ΔTV after 1 week (116 vs. 273 mm³, p=0.005) and 2 weeks of treatment (657 vs 1545 mm³, p=0.01). Compared to Sorafenib alone, the combination group exhibited a lower ΔTV after 1 week (116 vs 238 mm³, p=0.01), 2 weeks (657 vs 1320 mm³_,p=0.01), and 3 weeks of treatment (1738 vs 5405 mm³, p=0.01).

Conclusion:

Systemic administration of eNK cells with Sorafenib resulted in a diminished ΔTV compared to standard-of-care Sorafenib monotherapy. These results emphasize the synergistic effects of systemic eNK cell immunotherapy with Sorafenib for HCC while underscoring the need to incorporate tumor volume as a metric for treatment response.