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Rapid generation of human recombinant monoclonal antibodies from antibody-secreting cells using ferrofluid-based technology.
Strazza, Veronica; Rossi, Marco; Avati, Andrea; Tiseo, Giusy; Falcone, Marco; Cusi, Maria Grazia; Menichetti, Francesco; Ricciardi-Castagnoli, Paola; Tinti, Cristina; Pileri, Piero.
Afiliación
  • Strazza V; Hyper Antibody Research & Development (HARD) -Lab, Toscana Life Sciences Foundation, Siena, Italy.
  • Rossi M; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
  • Avati A; Hyper Antibody Research & Development (HARD) -Lab, Toscana Life Sciences Foundation, Siena, Italy.
  • Tiseo G; Hyper Antibody Research & Development (HARD) -Lab, Toscana Life Sciences Foundation, Siena, Italy.
  • Falcone M; Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
  • Cusi MG; Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
  • Menichetti F; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Ricciardi-Castagnoli P; Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
  • Tinti C; Hyper Antibody Research & Development (HARD) -Lab, Toscana Life Sciences Foundation, Siena, Italy.
  • Pileri P; Hyper Antibody Research & Development (HARD) -Lab, Toscana Life Sciences Foundation, Siena, Italy.
Front Immunol ; 15: 1341389, 2024.
Article en En | MEDLINE | ID: mdl-38698845
ABSTRACT
Monoclonal antibodies (mAbs) are one of the most important classes of biologics with high therapeutic and diagnostic value, but traditional methods for mAbs generation, such as hybridoma screening and phage display, have limitations, including low efficiency and loss of natural chain pairing. To overcome these challenges, novel single B cell antibody technologies have emerged, but they also have limitations such as in vitro differentiation of memory B cells and expensive cell sorters. In this study, we present a rapid and efficient workflow for obtaining human recombinant monoclonal antibodies directly from single antigen-specific antibody secreting cells (ASCs) in the peripheral blood of convalescent COVID-19 patients using ferrofluid technology. This process allows the identification and expression of recombinant antigen-specific mAbs in less than 10 days, using RT-PCR to generate linear Ig heavy and light chain gene expression cassettes, called "minigenes", for rapid expression of recombinant antibodies without cloning procedures. This approach has several advantages. First, it saves time and resources by eliminating the need for in vitro differentiation. It also allows individual antigen-specific ASCs to be screened for effector function prior to recombinant antibody cloning, enabling the selection of mAbs with desired characteristics and functional activity. In addition, the method allows comprehensive analysis of variable region repertoires in combination with functional assays to evaluate the specificity and function of the generated antigen-specific antibodies. Our approach, which rapidly generates recombinant monoclonal antibodies from single antigen-specific ASCs, could help to identify functional antibodies and deepen our understanding of antibody dynamics in the immune response through combined antibody repertoire sequence analysis and functional reactivity testing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes / SARS-CoV-2 / COVID-19 / Anticuerpos Monoclonales / Células Productoras de Anticuerpos Límite: Female / Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes / SARS-CoV-2 / COVID-19 / Anticuerpos Monoclonales / Células Productoras de Anticuerpos Límite: Female / Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza