Enhanced Natural Killer Cell Immunotherapy by Rationally Assembling Fc Fragments of Antibodies onto Tumor Membranes

Tianjiao Ji, Jiayan Lang, Bo Ning, Feifei Qi, Hui Wang, Yinlong Zhang, Ruifang Zhao, Xiao Yang, Lijing Zhang, Wei Li, Xinghua Shi, Zhihai Qin, Ying Zhao, Guangjun Nie

Research output: Contribution to journalArticle

Abstract

Recent advances in cancer immunotherapy have exploited the efficient potential of natural killer (NK) cells to kill tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC). However, this therapeutic strategy is seriously limited by tumor antigen heterogeneity since antibodies can only recognize specific antigens. In this work, modified antibodies or their Fc fragments that can target solid tumors without the necessity of specific antigen presentation on tumors are developed. Briefly, Fc fragments or therapeutic monoclonal antibodies are conjugated with the N-terminus of pH low insertion peptide so that they will selectively assemble onto the membrane of solid tumor cells via the conformational transformation of the peptide by responding to the acidic tumor microenvironment. The inserted Fc fragments or antibodies can efficiently activate NK cells, initiating ADCC and killing multiple types of tumor cells, including antigen-negative cancer cells. In vivo therapeutic results also exhibit significant efficacy on both primary solid tumors and tumor metastasis. These modified Fc fragments and antibodies present strong potential to overcome the limitation of tumor antigen heterogeneity, broadening the applications of NK cell immunotherapy on solid tumor treatment.

Original languageEnglish (US)
Article number1804395
JournalAdvanced Materials
Volume31
Issue number6
DOIs
StatePublished - Feb 8 2019

Fingerprint

Neoplasm Antibodies
Immunoglobulin Fc Fragments
Antibodies
Tumors
Membranes
Antigens
Cells
Neoplasm Antigens
Cytotoxicity
Peptides
Monoclonal antibodies
Monoclonal Antibodies

Keywords

  • Fc fragment of antibodies
  • NK cell immunotherapy
  • pHLIP
  • solid tumors
  • targeted ADCC

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

Cite this

Enhanced Natural Killer Cell Immunotherapy by Rationally Assembling Fc Fragments of Antibodies onto Tumor Membranes. / Ji, Tianjiao; Lang, Jiayan; Ning, Bo; Qi, Feifei; Wang, Hui; Zhang, Yinlong; Zhao, Ruifang; Yang, Xiao; Zhang, Lijing; Li, Wei; Shi, Xinghua; Qin, Zhihai; Zhao, Ying; Nie, Guangjun.

In: Advanced Materials, Vol. 31, No. 6, 1804395, 08.02.2019.

Research output: Contribution to journalArticle

Ji, T, Lang, J, Ning, B, Qi, F, Wang, H, Zhang, Y, Zhao, R, Yang, X, Zhang, L, Li, W, Shi, X, Qin, Z, Zhao, Y & Nie, G 2019, 'Enhanced Natural Killer Cell Immunotherapy by Rationally Assembling Fc Fragments of Antibodies onto Tumor Membranes', Advanced Materials, vol. 31, no. 6, 1804395. https://doi.org/10.1002/adma.201804395
Ji, Tianjiao ; Lang, Jiayan ; Ning, Bo ; Qi, Feifei ; Wang, Hui ; Zhang, Yinlong ; Zhao, Ruifang ; Yang, Xiao ; Zhang, Lijing ; Li, Wei ; Shi, Xinghua ; Qin, Zhihai ; Zhao, Ying ; Nie, Guangjun. / Enhanced Natural Killer Cell Immunotherapy by Rationally Assembling Fc Fragments of Antibodies onto Tumor Membranes. In: Advanced Materials. 2019 ; Vol. 31, No. 6.
@article{b06ec8bbf9da482f9e4cd7045475c6d1,
title = "Enhanced Natural Killer Cell Immunotherapy by Rationally Assembling Fc Fragments of Antibodies onto Tumor Membranes",
abstract = "Recent advances in cancer immunotherapy have exploited the efficient potential of natural killer (NK) cells to kill tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC). However, this therapeutic strategy is seriously limited by tumor antigen heterogeneity since antibodies can only recognize specific antigens. In this work, modified antibodies or their Fc fragments that can target solid tumors without the necessity of specific antigen presentation on tumors are developed. Briefly, Fc fragments or therapeutic monoclonal antibodies are conjugated with the N-terminus of pH low insertion peptide so that they will selectively assemble onto the membrane of solid tumor cells via the conformational transformation of the peptide by responding to the acidic tumor microenvironment. The inserted Fc fragments or antibodies can efficiently activate NK cells, initiating ADCC and killing multiple types of tumor cells, including antigen-negative cancer cells. In vivo therapeutic results also exhibit significant efficacy on both primary solid tumors and tumor metastasis. These modified Fc fragments and antibodies present strong potential to overcome the limitation of tumor antigen heterogeneity, broadening the applications of NK cell immunotherapy on solid tumor treatment.",
keywords = "Fc fragment of antibodies, NK cell immunotherapy, pHLIP, solid tumors, targeted ADCC",
author = "Tianjiao Ji and Jiayan Lang and Bo Ning and Feifei Qi and Hui Wang and Yinlong Zhang and Ruifang Zhao and Xiao Yang and Lijing Zhang and Wei Li and Xinghua Shi and Zhihai Qin and Ying Zhao and Guangjun Nie",
year = "2019",
month = "2",
day = "8",
doi = "10.1002/adma.201804395",
language = "English (US)",
volume = "31",
journal = "Advanced Materials",
issn = "0935-9648",
publisher = "Wiley-VCH Verlag",
number = "6",

}

TY - JOUR

T1 - Enhanced Natural Killer Cell Immunotherapy by Rationally Assembling Fc Fragments of Antibodies onto Tumor Membranes

AU - Ji, Tianjiao

AU - Lang, Jiayan

AU - Ning, Bo

AU - Qi, Feifei

AU - Wang, Hui

AU - Zhang, Yinlong

AU - Zhao, Ruifang

AU - Yang, Xiao

AU - Zhang, Lijing

AU - Li, Wei

AU - Shi, Xinghua

AU - Qin, Zhihai

AU - Zhao, Ying

AU - Nie, Guangjun

PY - 2019/2/8

Y1 - 2019/2/8

N2 - Recent advances in cancer immunotherapy have exploited the efficient potential of natural killer (NK) cells to kill tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC). However, this therapeutic strategy is seriously limited by tumor antigen heterogeneity since antibodies can only recognize specific antigens. In this work, modified antibodies or their Fc fragments that can target solid tumors without the necessity of specific antigen presentation on tumors are developed. Briefly, Fc fragments or therapeutic monoclonal antibodies are conjugated with the N-terminus of pH low insertion peptide so that they will selectively assemble onto the membrane of solid tumor cells via the conformational transformation of the peptide by responding to the acidic tumor microenvironment. The inserted Fc fragments or antibodies can efficiently activate NK cells, initiating ADCC and killing multiple types of tumor cells, including antigen-negative cancer cells. In vivo therapeutic results also exhibit significant efficacy on both primary solid tumors and tumor metastasis. These modified Fc fragments and antibodies present strong potential to overcome the limitation of tumor antigen heterogeneity, broadening the applications of NK cell immunotherapy on solid tumor treatment.

AB - Recent advances in cancer immunotherapy have exploited the efficient potential of natural killer (NK) cells to kill tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC). However, this therapeutic strategy is seriously limited by tumor antigen heterogeneity since antibodies can only recognize specific antigens. In this work, modified antibodies or their Fc fragments that can target solid tumors without the necessity of specific antigen presentation on tumors are developed. Briefly, Fc fragments or therapeutic monoclonal antibodies are conjugated with the N-terminus of pH low insertion peptide so that they will selectively assemble onto the membrane of solid tumor cells via the conformational transformation of the peptide by responding to the acidic tumor microenvironment. The inserted Fc fragments or antibodies can efficiently activate NK cells, initiating ADCC and killing multiple types of tumor cells, including antigen-negative cancer cells. In vivo therapeutic results also exhibit significant efficacy on both primary solid tumors and tumor metastasis. These modified Fc fragments and antibodies present strong potential to overcome the limitation of tumor antigen heterogeneity, broadening the applications of NK cell immunotherapy on solid tumor treatment.

KW - Fc fragment of antibodies

KW - NK cell immunotherapy

KW - pHLIP

KW - solid tumors

KW - targeted ADCC

UR - http://www.scopus.com/inward/record.url?scp=85058448540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058448540&partnerID=8YFLogxK

U2 - 10.1002/adma.201804395

DO - 10.1002/adma.201804395

M3 - Article

VL - 31

JO - Advanced Materials

JF - Advanced Materials

SN - 0935-9648

IS - 6

M1 - 1804395

ER -