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Recombinant monoclonal antibodies for therapeutic use

Grant number: 19/10724-2
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Start date: June 01, 2019
End date: December 31, 2021
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Ana Maria Moro
Grantee:João Victor Batalha de Carvalho
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:15/15611-0 - Recombinant monoclonal antibodies for therapeutic use, AP.TEM

Abstract

CD3 is a set of three protein chains associated with TCR±:² chains on the T lymphocytes membrane. The CD3 complex is essential for T cells activation and even for its the correct TCR expression. Anti-CD3 monoclonal antibodies (mAbs) have a great potential to treatment autoimmune diseases and induction of tolerance to allogeneic transplants. The original anti- CD3 mAb, produced by a murine hybridoma, present a limited therapeutic use due to adverse reactions induction like T cells proliferation and pro-inflammatory cytokines secretion (i.e. IFN-c and TNF-±). Aiming to avoid immunogenicity issues with non-human molecules, several anti-CD3 mAbs were humanized. The experimental uses of the humanized anti-CD3 mAbs have been associated with increase of both regulatory T lymphocytes (Treg) and immunoregulatory cytokines (i.e. TGF-² and IL-10). To test the immunomodulation potential of clones of humanized anti-CD3 developed at Butantan Institute, São Paulo - SP, this project proposes in vitro assays with lymphocytes from human peripheral blood stimulated by the humanized antibody. The regulator profile x pro-inflammatory profile will be evaluated by the capacity of the antibody to reduce the effector T cells and increase Tregs cellular proliferation. The pattern of secreted cytokines will be assessed by flow cytometry and the expression of regulatory/pro-inflammatory genes by real time PCR. Anti-CD3 induced Tregs will be tested in an in vitro inhibition assay of human effector lymphocytes. All results will be compared with the original murine correspondent expecting to induction a regulatory response by the humanized anti-CD3. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MANIERI, TANIA MARIA; TAKATA, DANIELA YUMI; TARGINO, ROSELAINE CAMPOS; QUINTILIO, WAGNER; BATALHA-CARVALHO, JOAO VICTOR; LUCIA DA SILVA, CAMILA MARIA; MORO, ANA MARIA. Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines. PHARMACEUTICS, v. 14, n. 10, p. 16-pg., . (20/07040-1, 19/10724-2, 15/15611-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CARVALHO, João Victor Batalha de. HUMANIZED MONOCLONAL ANTIBODY ANTI-CD3: obtaining and physico-chemical and functional caracterization with evaluation of the immunoregulatory profile. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.