한빛사 논문
Sao Puth a,b,c,1, Vivek Verma a,1,2, Seol Hee Hong a,d,e, Wenzhi Tan a,c,3, Shee Eun Lee a,d,e,*, Joon Haeng Rhee a,b,c,d,*
a Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun, Jeonnam, 58128, Republic of Korea b Combinatorial Tumor Immunotherapy MRC, Chonnam National University Medical School, Hwasun-gun, Jeonnam, 58128, Republic of Korea c Department of Microbiology, Chonnam National University Medical School, Hwasun-gun, Jeonnam, 58128, Republic of Korea d Immunotherapy Innovation Center, Hwasun-gun, Jeonnam, 58128, Republic of Korea e Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea
* Corresponding author.
1 These authors contributed equally to this work.
2 Current affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. 3 Current affiliation: School of Biomedical Sciences, Hunan University, Changsha, Hunan 410082, China.
Abstract
Therapeutic cancer vaccines (TCVs) should induce robust tumor-specific T cell responses. To achieve this, TCVs incorporate T cell epitopes and strong adjuvants. Here, we report an all-in-one adjuvanted cancer vaccine platform that targets the intracellular compartment of dentritic cells and subsequently induces effective cytotoxic T cell responses. We screened a novel peptide (DCpep6) that specifically binds and transmits into CD11c+ cells through a novel in vivo phage biopanning. We then engineered a protein-based TCV (DEF) consisting of DCpep6 (D), an optimized HPV E7 tumor antigen (E), and a built-in flagellin adjuvant (F) as a single molecule. DEF was stably expressed, and each component was functional. In vivo-administered DEF rapidly biodistributed in draining LNs and internalized into CD11c+ cells. DEF immunization elicited strong antitumor T cell responses and provided long-term survival of TC-1 tumor-implanted mice. The DEF-mediated antitumor effect was abolished in NLRC4−/− mice. Taken together, we propose a protein-based all-in-one TCV platform that intracellularly codelivers tumor antigen and inflammasome activator to DCs to induce long-lasting antitumor T cell responses.
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