Bi/tri-specific antibodies (HN-Fc-CD16 and HN-Fc-IL-15-CD16) cross-linking natural killer (NK)-CD16 and Newcastle Disease Virus (NDV)-HN, enhanced NK activation for cancer immunotherapy

Mina Bahrololoumi Shapourabadi; Frank Momburg; Farzin Roohvand; Mostafa Jarahian; Nasir Mohajel; Arash Arashkia; Fatemeh Hajari Taheri; Maryam Abbasalipour; Kayhan Azadmanesh

doi:10.1016/j.intimp.2021.107762

Bi/tri-specific antibodies (HN-Fc-CD16 and HN-Fc-IL-15-CD16) cross-linking natural killer (NK)-CD16 and Newcastle Disease Virus (NDV)-HN, enhanced NK activation for cancer immunotherapy

Int Immunopharmacol. 2021 Jul:96:107762. doi: 10.1016/j.intimp.2021.107762. Epub 2021 May 31.

Authors

Mina Bahrololoumi Shapourabadi¹, Frank Momburg², Farzin Roohvand³, Mostafa Jarahian⁴, Nasir Mohajel⁵, Arash Arashkia⁶, Fatemeh Hajari Taheri⁷, Maryam Abbasalipour⁸, Kayhan Azadmanesh⁹

Affiliations

¹ Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: minabahrololoumi@gmail.com.
² Antigen Presentation & T/NK Cell Unit, Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: f.momburg@dkfz-heidelberg.de.
³ Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: rfarzin@pasteur.ac.ir.
⁴ Antigen Presentation & T/NK Cell Unit, Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: mostafajarahian@gmail.com.
⁵ Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: n_mohajel@pasteur.ac.ir.
⁶ Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: a_arashkia@pasteur.ac.ir.
⁷ Department of Immunology, Hybridoma Lab, Pasteur Institute of Iran, Tehran, Iran. Electronic address: f.h.taheri@gmail.com.
⁸ Department of Molecular Medicine, Biotechnology Research Centre, Pasteur Institute of Iran, Tehran, Iran. Electronic address: m.abbasalipour@gmail.com.
⁹ Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: azadmanesh@pasteur.ac.ir.

PMID: 34162140
DOI: 10.1016/j.intimp.2021.107762

Abstract

Cancer/tumor cells infected with the "avian paramyxovirus Newcastle Disease Virus (TC-NDV)" express the viral hemagglutinin-neuraminidase (HN) on the cell surface that is used as both the danger signal and anchor for bi/tri-specific antibodies (bs/tsAbs).We constructed a bs-Ab (HN-Fc-CD16) that bindsto HN and natural killer (NK)-CD16 receptor (FcgRIII)and a ts-Ab (HN-Fc-IL15-CD16) harbouring NK-activating cytokine "IL-15" within the bs-Ab.In silicoand computational predictions indicated proper exposure of both Abs in bs/tsAbs.Properbinding of thebi/tsAbstoHN on surface of TC-NDVandCD16⁺-cells was demonstrated by flow cytometry.The bi/tsAbstriggeredspecificcytotoxicity of NK cells againstTC-NDVand elicited substantial IFN-γproduction by activated NK cells(higher for ts-Ab) that sound promising for cancer immunotherapy purposes.

Keywords: Bispecific antibody; Immunotherapy; Mammalian expression system; Natural Killer cell (NK cell); Newcastle Disease Virus (NDV); Trispecific antibody.

MeSH terms

Antibodies, Bispecific / biosynthesis*
Antibodies, Bispecific / chemistry
Antibodies, Bispecific / immunology
Antibodies, Bispecific / pharmacology*
Antineoplastic Agents, Immunological / chemistry
Antineoplastic Agents, Immunological / immunology
Antineoplastic Agents, Immunological / pharmacology*
Binding Sites
Cytotoxicity Tests, Immunologic
HEK293 Cells
HN Protein / immunology*
HeLa Cells
Humans
Immunoglobulin Fc Fragments / immunology
Immunotherapy / methods
Interferon-gamma / metabolism
Killer Cells, Natural / immunology
Ligands
Models, Molecular
Neoplasms / immunology
Neoplasms / therapy*
Newcastle disease virus / immunology*
Receptors, IgG / immunology*

Substances

Antibodies, Bispecific
Antineoplastic Agents, Immunological
HN Protein
Immunoglobulin Fc Fragments
Ligands
Receptors, IgG
Interferon-gamma