MRI-guided interventional natural killer cell delivery for liver tumor treatment

Zhanliang Su, Xifu Wang, Linfeng Zheng, Tianchu Lyu, Matteo Figini, Bin Wang, Daniele Procissi, Junjie Shangguan, Chong Sun, Liang Pan, Lei Qin, Bin Zhang, Yury Velichko, Riad Salem, Vahid Yaghmai, Andrew Christian Larson, Zhuoli Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

While natural killer (NK) cell-based adoptive transfer immunotherapy (ATI) provides only modest clinical success in cancer patients. This study was hypothesized that MRI-guided transcatheter intra-hepatic arterial (IHA) infusion permits local delivery to liver tumors to improve outcomes during NK-based ATI in a rat model of hepatocellular carcinoma (HCC). Mouse NK cells were labeled with clinically applicable iron nanocomplexes. Twenty rat HCC models were assigned to three groups: transcatheter IHA saline infusion as the control group, transcatheter IHA NK infusion group, and intravenous (IV) NK infusion group. MRI studies were performed at baseline and at 24 h, 48 h, and 8 days postinfusion. There was a significant difference in tumor R2* values between baseline and 24 h following the selective transcatheter IHA NK delivery to the tumors (P = 0.039) when compared to IV NK infusion (P = 0.803). At 8 days postinfusion, there were significant differences in tumor volumes between the control, IV, and IHA NK infusion groups (control vs. IV, P = 0.196; control vs. IHA, P < 0.001; and IV vs. IHA, P = 0.001). Moreover, there was a strong correlation between tumor R2* value change (∆R2*) at 24 h postinfusion and tumor volume change (∆volume) at 8 days in IHA group (R2 = 0.704, P < 0.001). Clinically applicable labeled NK cells with 12-h labeling time can be tracked by MRI. Transcatheter IHA infusion improves NK cell homing efficacy and immunotherapeutic efficiency. The change in tumor R2* value 24 h postinfusion is an important early biomarker for prediction of longitudinal response.

Original languageEnglish (US)
Pages (from-to)1860-1869
Number of pages10
JournalCancer medicine
Volume7
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Interventional Magnetic Resonance Imaging
Natural Killer Cells
Liver
Neoplasms
Adoptive Immunotherapy
Therapeutics
Intra Arterial Infusions
Adoptive Transfer
Tumor Burden
Hepatocellular Carcinoma
Control Groups
Intravenous Infusions

Keywords

  • Adoptive transfer immunotherapy
  • hepatocellular carcinoma
  • interventional oncology
  • magnetic resonance imaging
  • natural killer cell

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Su, Zhanliang ; Wang, Xifu ; Zheng, Linfeng ; Lyu, Tianchu ; Figini, Matteo ; Wang, Bin ; Procissi, Daniele ; Shangguan, Junjie ; Sun, Chong ; Pan, Liang ; Qin, Lei ; Zhang, Bin ; Velichko, Yury ; Salem, Riad ; Yaghmai, Vahid ; Larson, Andrew Christian ; Zhang, Zhuoli. / MRI-guided interventional natural killer cell delivery for liver tumor treatment. In: Cancer medicine. 2018 ; Vol. 7, No. 5. pp. 1860-1869.
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abstract = "While natural killer (NK) cell-based adoptive transfer immunotherapy (ATI) provides only modest clinical success in cancer patients. This study was hypothesized that MRI-guided transcatheter intra-hepatic arterial (IHA) infusion permits local delivery to liver tumors to improve outcomes during NK-based ATI in a rat model of hepatocellular carcinoma (HCC). Mouse NK cells were labeled with clinically applicable iron nanocomplexes. Twenty rat HCC models were assigned to three groups: transcatheter IHA saline infusion as the control group, transcatheter IHA NK infusion group, and intravenous (IV) NK infusion group. MRI studies were performed at baseline and at 24 h, 48 h, and 8 days postinfusion. There was a significant difference in tumor R2* values between baseline and 24 h following the selective transcatheter IHA NK delivery to the tumors (P = 0.039) when compared to IV NK infusion (P = 0.803). At 8 days postinfusion, there were significant differences in tumor volumes between the control, IV, and IHA NK infusion groups (control vs. IV, P = 0.196; control vs. IHA, P < 0.001; and IV vs. IHA, P = 0.001). Moreover, there was a strong correlation between tumor R2* value change (∆R2*) at 24 h postinfusion and tumor volume change (∆volume) at 8 days in IHA group (R2 = 0.704, P < 0.001). Clinically applicable labeled NK cells with 12-h labeling time can be tracked by MRI. Transcatheter IHA infusion improves NK cell homing efficacy and immunotherapeutic efficiency. The change in tumor R2* value 24 h postinfusion is an important early biomarker for prediction of longitudinal response.",
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author = "Zhanliang Su and Xifu Wang and Linfeng Zheng and Tianchu Lyu and Matteo Figini and Bin Wang and Daniele Procissi and Junjie Shangguan and Chong Sun and Liang Pan and Lei Qin and Bin Zhang and Yury Velichko and Riad Salem and Vahid Yaghmai and Larson, {Andrew Christian} and Zhuoli Zhang",
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Su, Z, Wang, X, Zheng, L, Lyu, T, Figini, M, Wang, B, Procissi, D, Shangguan, J, Sun, C, Pan, L, Qin, L, Zhang, B, Velichko, Y, Salem, R, Yaghmai, V, Larson, AC & Zhang, Z 2018, 'MRI-guided interventional natural killer cell delivery for liver tumor treatment', Cancer medicine, vol. 7, no. 5, pp. 1860-1869. https://doi.org/10.1002/cam4.1459

MRI-guided interventional natural killer cell delivery for liver tumor treatment. / Su, Zhanliang; Wang, Xifu; Zheng, Linfeng; Lyu, Tianchu; Figini, Matteo; Wang, Bin; Procissi, Daniele; Shangguan, Junjie; Sun, Chong; Pan, Liang; Qin, Lei; Zhang, Bin; Velichko, Yury; Salem, Riad; Yaghmai, Vahid; Larson, Andrew Christian; Zhang, Zhuoli.

In: Cancer medicine, Vol. 7, No. 5, 01.05.2018, p. 1860-1869.

Research output: Contribution to journalArticle

TY - JOUR

T1 - MRI-guided interventional natural killer cell delivery for liver tumor treatment

AU - Su, Zhanliang

AU - Wang, Xifu

AU - Zheng, Linfeng

AU - Lyu, Tianchu

AU - Figini, Matteo

AU - Wang, Bin

AU - Procissi, Daniele

AU - Shangguan, Junjie

AU - Sun, Chong

AU - Pan, Liang

AU - Qin, Lei

AU - Zhang, Bin

AU - Velichko, Yury

AU - Salem, Riad

AU - Yaghmai, Vahid

AU - Larson, Andrew Christian

AU - Zhang, Zhuoli

PY - 2018/5/1

Y1 - 2018/5/1

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AB - While natural killer (NK) cell-based adoptive transfer immunotherapy (ATI) provides only modest clinical success in cancer patients. This study was hypothesized that MRI-guided transcatheter intra-hepatic arterial (IHA) infusion permits local delivery to liver tumors to improve outcomes during NK-based ATI in a rat model of hepatocellular carcinoma (HCC). Mouse NK cells were labeled with clinically applicable iron nanocomplexes. Twenty rat HCC models were assigned to three groups: transcatheter IHA saline infusion as the control group, transcatheter IHA NK infusion group, and intravenous (IV) NK infusion group. MRI studies were performed at baseline and at 24 h, 48 h, and 8 days postinfusion. There was a significant difference in tumor R2* values between baseline and 24 h following the selective transcatheter IHA NK delivery to the tumors (P = 0.039) when compared to IV NK infusion (P = 0.803). At 8 days postinfusion, there were significant differences in tumor volumes between the control, IV, and IHA NK infusion groups (control vs. IV, P = 0.196; control vs. IHA, P < 0.001; and IV vs. IHA, P = 0.001). Moreover, there was a strong correlation between tumor R2* value change (∆R2*) at 24 h postinfusion and tumor volume change (∆volume) at 8 days in IHA group (R2 = 0.704, P < 0.001). Clinically applicable labeled NK cells with 12-h labeling time can be tracked by MRI. Transcatheter IHA infusion improves NK cell homing efficacy and immunotherapeutic efficiency. The change in tumor R2* value 24 h postinfusion is an important early biomarker for prediction of longitudinal response.

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KW - interventional oncology

KW - magnetic resonance imaging

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