| Grant number: | 15/15611-0 |
| Support Opportunities: | Research Projects - Thematic Grants |
| Duration: | April 01, 2016 - December 31, 2021 |
| Field of knowledge: | Biological Sciences - Immunology - Applied Immunology |
| Principal Investigator: | Ana Maria Moro |
| Grantee: | Ana Maria Moro |
| Host Institution: | Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| Associated researchers: | Jane Zveiter de Moraes ; Jorge Elias Kalil Filho ; Lilian Rumi Tsuruta Sagawa ; Mariana Lopes dos Santos ; Paulo Lee Ho ; Roger Chammas ; Verônica Porto Carreiro de Vasconcellos Coelho ; Wagner Quintilio |
| Associated scholarship(s): | 20/08382-3 - Recombinant monoclonal antibodies for therapeutic use,
BP.TT 20/06615-0 - Recombinant monoclonal antibodies for therapeutic use, BP.TT 19/17300-3 - Recombinant monoclonal antibodies for therapeutic use, BP.TT + associated scholarships - associated scholarships |
Abstract
Antibodies are considered magic bullets, and monoclonal antibodies (mAbs), displaying fine specificity binding for the target, represent today a great clinical and commercial success. There are currently 48 approved mAbs for therapeutic use, 26 targeted to cancer treatment, 10 targeted to auto-immune diseases, 12 targeted to antigens related to other clinical situations and hundreds in different phases of clinical trials. In the last decades technologies were developed that assured the state of art, starting with chimeric and followed by humanized and fully human antibodies. This thematic project is focused on the development and obtainment of recombinant mAbs in different formats, by different technologies, aimed to different clinical applications: (1) anti-digoxin Fab fragment variants generated by phage display, with potential to counteract intoxication by digitalis; (2) humanized anti-CD3 mAbs for induction of tolerance in transplantation and control of autoimmune diseases as diabetes type 1; (3) anti-TNF± biosimilar mAb and possibly a biobetter version for rheumatoid arthritis treatment and other autoimmune diseases; (4) humanization of an anti-FGF2 mAb that demonstrated with its murine version a reduction in nodules and vascularization in a melanoma model in mice; (5) library of human antibodies sequences; (6) neutralizing human anti-tetanus mAbs as substitute for heterologous polyclonal antibodies and as a model for platform implementation for other human mAbs. Besides the generation of cell lines producing recombinant mAbs, including selection and analytic characterization for antibodies with therapeutic potential, this project proposes the optimization of antibodies production by selection of culture media and cultivation modes, in preparation to scaling-up. (AU)
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