Human Ferritin Platform and Its Optimized Structures to Enhance Anti-Cancer Immunity

Bo Ram Lee, Hyo Jung Lee, June Huh, Chul Joo Yoon, Se Jin Oh, Kwon Ho Song, Sojin Jeong, Jungwon Kim, Kyung Mi Lee, Beom Soo Shin, Ji Hoon Jeong, Tae Woo Kim, Jeewon Lee

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Although anti-cancer vaccination and immune checkpoint (IC) therapy have emerged as potent cancer treatment modalities, their application remains limited to a subset of patients due to vaccine adjuvant toxicities and IC-blocking antibody-associated systemic immune adverse events. Here, an innovative platform is reported for adjuvant- and antibody-free cancer immunotherapy using human heavy chain ferritin (huHF)-derived optimally designed structures presenting multiple-copies of tumor-specific antigens (TSAs) or IC molecules (ICMs) on their surface. Through structure-guided molecular design, TSA-presenting huHFs for targeting TSAs at dendritic cells (DCs) are constructed with preservation of huHF-intrinsic affinity for transferrin receptors on DCs, and multi-copies of an ICM are also presented on huHF for blocking a cognate regulatory IC. The adjuvant-free co-administration of TSA- and ICM-presenting huHFs effectively elicits TSA-specific CD8+ T cell activation, strikingly suppresses both tumor growth and interleukin 17+ CD4+ T cell responses, and generates long-lasting protective immunity, indicating that this novel approach offers a promising breakthrough in cancer immunotherapy.

Original languageEnglish
Article number2000208
JournalAdvanced Therapeutics
Volume4
Issue number2
DOIs
Publication statusPublished - 2021 Feb

Keywords

  • anti-tumor immunity
  • cancer immunotherapy
  • human heavy chain ferritin
  • molecular design

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Pharmaceutical Science
  • Genetics(clinical)
  • Biochemistry, medical
  • Pharmacology (medical)

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