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Article

MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models

1
Hepatitis Research Center, Department of Surgery, National Taiwan University Hospital, College of Medicine, Taipei 100, Taiwan
2
Centre of Mini-Invasive Interventional Oncology, National Taiwan University Hospital, Taipei 100, Taiwan
3
MiNA Therapeutics Ltd., London W12 0BZ, UK
4
Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK
5
Department of Haemato-Oncology, National University Cancer Institute, Singapore 119077, Singapore
6
Department of General Surgery, University Hospital of Larissa, 41110 Larissa, Greece
7
Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Marieke F. Fransen
Int. J. Mol. Sci. 2021, 22(17), 9168; https://doi.org/10.3390/ijms22179168
Received: 25 July 2021 / Revised: 22 August 2021 / Accepted: 23 August 2021 / Published: 25 August 2021
(This article belongs to the Special Issue Immunological Responses to Cancer Therapy)
The transcription factor CEBPA is a master regulator of liver homeostasis, myeloid cell differentiation and is downregulated in several oncogenic diseases. MTL-CEBPA is a small activating RNA drug which upregulates gene expression of CEBPA for treatment of hepatocellular carcinoma (HCC). We investigate whether MTL-CEBPA has immune modulatory effects by combining MTL-CEBPA with an anti-PD-1 checkpoint inhibitor (CPI) and/or radiofrequency ablation (RFA) in two preclinical models. First, mice with two flanks of HCC tumors (BNL) were treated with combinations of RFA (right flank), anti-PD-1 or MTL-CEBPA. The reduction of the left flank tumors was most pronounced in the group treated with RFA+anti-PD1+MTL-CEBPA and 7/8 animals responded. This was the only group with a significant increase in CD8+ and CD49b+/CD45+ tumor infiltrating lymphocytes (TIL). Second, a combination of anti-PD-1+MTL-CEBPA was tested in a CT26 colon cancer model and this treatment significantly reduced tumor size, modulated the tumor immune microenvironment and increased TILs. These data suggest a clinical role for combination treatment with CPIs, RFA and MTL-CEBPA through synergistic priming of the immune tumor response, enabling RFA and CPIs to have a pronounced anti-tumor effect including activity in non-treated tumors in the case of RFA. View Full-Text
Keywords: CEBPA; abscopal; immunotherapy; PD-1 CEBPA; abscopal; immunotherapy; PD-1
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MDPI and ACS Style

Huang, K.-W.; Tan, C.P.; Reebye, V.; Chee, C.E.; Zacharoulis, D.; Habib, R.; Blakey, D.C.; Rossi, J.J.; Habib, N.; Sodergren, M.H. MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models. Int. J. Mol. Sci. 2021, 22, 9168. https://doi.org/10.3390/ijms22179168

AMA Style

Huang K-W, Tan CP, Reebye V, Chee CE, Zacharoulis D, Habib R, Blakey DC, Rossi JJ, Habib N, Sodergren MH. MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models. International Journal of Molecular Sciences. 2021; 22(17):9168. https://doi.org/10.3390/ijms22179168

Chicago/Turabian Style

Huang, Kai-Wen, Choon Ping Tan, Vikash Reebye, Cheng Ean Chee, Dimitris Zacharoulis, Robert Habib, David C. Blakey, John J. Rossi, Nagy Habib, and Mikael H. Sodergren. 2021. "MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models" International Journal of Molecular Sciences 22, no. 17: 9168. https://doi.org/10.3390/ijms22179168

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