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.

• Authors: 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
• Journal: Advanced materials (Deerfield Beach, Fla.) (Adv Mater) Vol. 31 Issue 6 Pg. e1804395 (Feb 2019) ISSN: 1521-4095 [Electronic] Germany
• PMID: 30549110 (Publication Type: Journal Article)
• Copyright: © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin Fc Fragments

Topics

• Animals
• Antibodies, Monoclonal (pharmacokinetics)
• Antibody-Dependent Cell Cytotoxicity (drug effects)
• Cell Line, Tumor
• Cell Membrane (drug effects)
• Cell Survival (drug effects)
• Humans
• Hydrogen-Ion Concentration
• Immunoglobulin Fc Fragments (pharmacology)
• Immunotherapy (methods)
• Killer Cells, Natural (drug effects)
• Mice
• Protein Conformation
• Protein Multimerization (drug effects)
• Signal Transduction
• Tumor Microenvironment