Improving of human fragment antibodies (scFvs) specific for animals' venoms

• Grant number: 18/14158-9
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 15, 2018
• End date: November 14, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Felipe Augusto Cerni
• Supervisor: Andreas Hougaard Laustsen
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Technical University of Denmark (DTU), Denmark
• Associated to the scholarship: 17/14035-1 - Improving of human fragment antibodies (scFvs) specific for animals' venoms, BP.PD

Abstract

The production of monoclonal antibodies (mAbs) was first described in 1975, with the discovery of the hybridoma technique. Although the hybridoma technique was described in 1975, only 10 years later, in 1985, the first monoclonal antibodies were released for therapeutic use in humans. However, only after the optimization of some techniques of these mAbs, the pharmaceutical market with monoclonal antibodies had a remarkable growth. Among the optimizations, we can highlight the recombinant DNA technology and the Phage Display technique. Recently, the representation of the monoclonal antibodies (whether murine, chimeric, humanized or human) in the pharmaceutical market is a reality, being used as the most advanced therapies for the treatment of a diversity of diseases (e.g. cancer, allergy, autoimmune diseases). With 47 mAbs already marketed in 2017, there is an expectation of more than 70 in 2020. Dr. Barbosa's group has been working with monoclonal human fragment antibodies targeting venoms for many years. Using Phage Display technology, the Barbosa's laboratory produced scFv (single-chain fragment variable) human antibodies to many venoms - Serrumab, Bothrumab, Crotumab, Lachesumab, Micrurumab and Afribumab. In this way, the group aim is to produce better antivenoms (new genetarion of antivenoms), in other words, to replace the use of heterologous antivenoms used for more than a century. However, before these antibodies reach the market, they still need to be improved regarding affinity, formats, as well as, they need some complementary tests. Therefore, the present study will improve the affinity and the formats of the Serrumab and Afribumab antibodies.

Scientific publications

(7)

(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)

PUCCA, MANUELA B.; CERNI, FELIPE A.; JANKE, RAHEL; BERMUDEZ-MENDEZ, ERICK; LEDSGAARD, LINE; BARBOSA, JOSE E.; LAUSTSEN, ANDREAS H.. History of Envenoming Therapy and Current Perspectives. FRONTIERS IN IMMUNOLOGY, v. 10, JUL 10 2019. (17/14035-1, 18/14158-9, 17/04724-4)

OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; ALEXANDRE-SILVA, GABRIEL M.; CERNI, FELIPE A.; CREMONEZ, CAROLINE M.; ARANTES, ELIANE C.; ZOTTICH, UMBERTO; PUCCA, MANUELA B.. Scorpion toxins targeting Kv1.3 channels: insights into immunosuppression. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 25, APR 15 2019. (18/21233-7, 17/14035-1, 18/14158-9, 17/03580-9)

BOLDRINI-FRANCA, JOHARA; PINHEIRO-JUNIOR, ERNESTO LOPES; PEIGNEUR, STEVE; PUCCA, MANUELA BERTO; CERNI, FELIPE AUGUSTO; BORGES, RAFAEL JUNQUEIRA; COSTA, TASSIA RAFAELLA; IMAI CARONE, SANTE EMMANUEL; DE MATTOS FONTES, MARCOS ROBERTO; SAMPAIO, SUELY VILELA; et al. Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities. SCIENTIFIC REPORTS, v. 10, n. 1, MAR 11 2020. (15/18432-0, 15/00740-0, 18/14158-9, 16/24191-8, 15/16714-8, 17/13485-3, 11/23236-4, 17/14035-1, 16/04761-4, 14/16182-3, 15/17286-0)

FIGUEIREDO BORDON, KARLA DE CASTRO; COLOGNA, CAMILA TAKENO; FORNARI-BALDO, ELISA CORREA; PINHEIRO-JUNIOR, ERNESTO LOPES; CERNI, FELIPE AUGUSTO; AMORIM, FERNANDA GOBBI; PINO ANJOLETTE, FERNANDO ANTONIO; CORDEIRO, FRANCIELLE ALMEIDA; WIEZEL, GISELE ADRIANO; CARDOSO, IARA AIME; et al. From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery. FRONTIERS IN PHARMACOLOGY, v. 11, JUL 24 2020. (17/14035-1, 17/00586-6, 18/14158-9, 19/10173-6, 18/21233-7, 17/04724-4, 13/26619-7, 16/04761-4, 17/03580-9, 13/26200-6)

PUCCA, MANUELA B.; AHMADI, SHIRIN; CERNI, FELIPE A.; LEDSGAARD, LINE; SORENSEN, V, CHRISTOFFER; MCGEOGHAN, FARRELL T. S.; STEWART, TRENTON; SCHOOF, ERWIN; LOMONTE, BRUNO; KELLER, ULRICH AUF DEM; et al. Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins. FRONTIERS IN PHARMACOLOGY, v. 11, MAY 7 2020. (17/04724-4, 17/14035-1, 18/14158-9)

CAMPOS, LUCAS B.; PUCCA, MANUELA B.; SILVA, LUCIANO C.; PESSENDA, GABRIELA; FILARDI, BRUNO A.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; LAUSTSEN, ANDREAS H.; ARANTES, ELIANE C.; BARBOSA, JOSE E.. Identification of cross-reactive human single-chain variable fragments against phospholipases A(2) from Lachesis muta and Bothrops spp venoms. Toxicon, v. 184, p. 116-121, SEP 2020. (17/04724-4, 17/14035-1, 18/14158-9, 17/03580-9)

PUCCA, MANUELA B.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; JENKINS, TIMOTHY P.; ARGEMI, LIDIA; SORENSEN, CHRISTOFFER V.; AHMADI, SHIRIN; BARBOSA, JOSE E.; LAUSTSEN, ANDREAS H.. Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy. FRONTIERS IN IMMUNOLOGY, v. 10, SEP 6 2019. (18/14158-9, 18/21233-7, 17/04724-4, 17/14035-1, 17/03580-9)