An all-in-one adjuvanted therapeutic cancer vaccine targeting dendritic cell cytosol induces long-lived tumor suppression through NLRC4 inflammasome activation

Sao Puth, Vivek Verma, Seol Hee Hong, Wenzhi Tan, Shee Eun Lee, Joon Haeng Rhee

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number121542
JournalBiomaterials
Volume286
DOIs
StatePublished - Jul 2022

Bibliographical note

Funding Information:
J.H.R. was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government ( MSIT ) ( NRF-2020R1A5A2031185 ), ( NRF-2017M3A9E2056372 ), and a grant from the National Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea { 1720120(HA17C0038) }. S.E.L. was supported by the National Research Foundation of Korea ( NRF ) grant funded by the Korean government ( MSIT ), ( NRF-2019R1A5A2027521 ), ( NRF-2020M3A9G3080282 ), and ( NRF-2019R1A2B5B01069981 ).

Publisher Copyright:
© 2022 The Authors

Keywords

  • All-in-one vaccine
  • DC-targeting peptide
  • Flagellin
  • In vivo biopanning
  • Long-term survival
  • NLRC4
  • Therapeutic cancer vaccine (TCV)

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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