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 language | English |
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Article number | 2000208 |
Journal | Advanced Therapeutics |
Volume | 4 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2021 Feb |
Bibliographical note
Publisher Copyright:© 2020 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH
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)