Year: 2017
Type: article
Abstract: // Zhen Han 1 , De Yang 1 , Anna Trivett 1 and Joost J. Oppenheim 1 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA Correspondence to: De Yang, email: // Joost J. Oppenheim, email: // Keywords : HMGN1, R848, anti-PD-L1, anti-CTLA4, cytoxan Received : April 19, 2017 Accepted : May 10, 2017 Published : July 18, 2017 Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as ‘TheraVac’) consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors. Importantly, the resultant tumor-free mice were resistant to re-challenge with Hepa1-6 hepatoma, not B16 melanoma, demonstrating the acquisition of hepatoma-specific immunity in the absence of any administered tumor antigen. Mechanistic studies showed that upon treatment with TheraVac, Hepa1-6-bearing mice generated increased Hepa1-6-specific CTLs in the draining lymph nodes and showed greatly upregulated expression of CXCL9, CXCL10, and IFN-γ and elevated infiltration of T lymphocytes in tumor tissues. Treatment of large Hepa1-6 hepatomas on one mouse flank also eliminated smaller (approximately 0.5 cm in diameter) hepatomas implanted on the other flank. Thus, TheraVac has potential as a curative immunotherapeutic regimen for the treatment of human HCC.
Source: Oncotarget
Authors: Zhen Han, De Yang, Anna Trivett, Joost J. Oppenheim
Institutions: National Cancer Institute, Center for Cancer Research
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2736365842