Human Ferritin Platform and Its Optimized Structures to Enhance Anti‐Cancer Immunity. Issue 2 (21st December 2020)

• Record Type: Journal Article
• Authors: Lee, Bo‐Ram; Lee, Hyo‐Jung; Huh, June; Yoon, Chul Joo; Oh, Se Jin; Song, Kwon‐Ho; Jeong, Sojin; Kim, Jungwon; Lee, Kyung‐Mi; Shin, Beom Soo; Jeong, Ji Hoon; Kim, Tae Woo; Lee, Jeewon
• Is Part Of: Advanced therapeutics. Volume 4:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-21
• Subjects: anti‐tumor immunity -- cancer immunotherapy -- human heavy chain ferritin -- molecular design; Therapeutics -- Periodicals; Pharmaceutical technology -- Periodicals; Pharmacogenetics -- Periodicals; 615.5
• DOI: 10.1002/adtp.202000208
• Languages: English
• ISSNs: 2366-3987

Abstract

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. Abstract : Tumor‐specific antigen (TSA)‐ or programmed cell death protein 1 (PD1)‐presenting human heavy chain ferritin (huHF) are constructed through structure‐guided design of huHF. The adjuvant‐free co‐administration of TSA‐ and PD1‐presenting huHFs to tumor‐bearing mice significantly activates TSA‐specific CD8+ T cells, suppresses tumor growth and interleukin17+ CD4+ T cell activity, and generates long‐lasting protective immunity, indicating a promising breakthrough in cancer immunotherapy.