TY - JOUR
T1 - Preclinical Development and Validation of Translational Temperature Sensitive Iodized Oil Emulsion Mediated Transcatheter Arterial Chemo-Immuno-Embolization for the Treatment of Hepatocellular Carcinoma
AU - Kim, Heegon
AU - Choi, Bongseo
AU - Mouli, Samdeep K.
AU - Choi, Hyunjun
AU - Harris, Kathleen R.
AU - Kulik, Laura M.
AU - Lewandowski, Robert J.
AU - Kim, Dong Hyun
N1 - Funding Information:
The financial support from the Society of Interventional Oncology (SIO) is greatly acknowledged. This work was supported by grants R01CA218659 and R01EB026207 from the National Cancer Institute and the National Institute of Biomedical Imaging and Bioengineering. This work was also supported by the Center for Translational Imaging and Mouse Histology and Phenotyping Laboratory at Northwestern University.
Publisher Copyright:
© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2023
Y1 - 2023
N2 - Herein a practical strategy for augmenting immune activation in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is presented. Pluronic F127 (PF127) is incorporated with Lipiodol (LPD) to achieve safe and effective delivery of therapeutic agents during transcatheter intra-arterial (IA) local delivery. Enhanced emulsion stability, IA infusion, embolic effect, safety, pharmacokinetics, and tumor response of Doxorubicin loaded PF127-LPD (Dox-PF127-LPD) for TACE in both in vitro and in vivo preclinical VX2 liver cancer rabbit model and N1S1 HCC rat model are demonstrated. Then, transcatheter arterial chemo-immuno-embolization (TACIE) combining TACE and local delivery of immune adjuvant (TLR9 agonist CpG oligodeoxynucleotide) is successfully performed using CpG-loaded Dox-PF127-LPD. Concurrent and safe local delivery of CpG and TACE during TACIE demonstrate leveraged TACE-induced immunogenic tumor microenvironment and augment systemic anti-tumor immunity in syngeneic N1S1 HCC rat model. Finally, the broad utility and enhanced therapeutic efficacy of TACIE are validated in the diethylnitrosamine-induced rat HCC model. TACIE using clinically established protocols and materials shall be a convenient and powerful therapeutic approach that can be translated to patients with HCC. The robust anti-cancer immunity and tumor regression of TACIE, along with its favorable safety profile, indicate its potential as a novel localized combination immunotherapy for HCC treatment.
AB - Herein a practical strategy for augmenting immune activation in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is presented. Pluronic F127 (PF127) is incorporated with Lipiodol (LPD) to achieve safe and effective delivery of therapeutic agents during transcatheter intra-arterial (IA) local delivery. Enhanced emulsion stability, IA infusion, embolic effect, safety, pharmacokinetics, and tumor response of Doxorubicin loaded PF127-LPD (Dox-PF127-LPD) for TACE in both in vitro and in vivo preclinical VX2 liver cancer rabbit model and N1S1 HCC rat model are demonstrated. Then, transcatheter arterial chemo-immuno-embolization (TACIE) combining TACE and local delivery of immune adjuvant (TLR9 agonist CpG oligodeoxynucleotide) is successfully performed using CpG-loaded Dox-PF127-LPD. Concurrent and safe local delivery of CpG and TACE during TACIE demonstrate leveraged TACE-induced immunogenic tumor microenvironment and augment systemic anti-tumor immunity in syngeneic N1S1 HCC rat model. Finally, the broad utility and enhanced therapeutic efficacy of TACIE are validated in the diethylnitrosamine-induced rat HCC model. TACIE using clinically established protocols and materials shall be a convenient and powerful therapeutic approach that can be translated to patients with HCC. The robust anti-cancer immunity and tumor regression of TACIE, along with its favorable safety profile, indicate its potential as a novel localized combination immunotherapy for HCC treatment.
KW - hepatocellular carcinoma
KW - immunotherapies
KW - interventional oncology
KW - local therapies
KW - transcatheter arterial chemoembolization
UR - http://www.scopus.com/inward/record.url?scp=85159838947&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85159838947&partnerID=8YFLogxK
U2 - 10.1002/adhm.202300906
DO - 10.1002/adhm.202300906
M3 - Article
C2 - 37163283
AN - SCOPUS:85159838947
SN - 2192-2640
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
ER -
