Production and Characterization of Novel Photoimmunoconjugates for HIV Photoimmunotherapy

• Grant number: 17/10910-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2017
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Francisco Eduardo Gontijo Guimaraes
• Grantee: Mohammad Sadraeian
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07276-1 - CEPOF - Optics and Photonic Research Center, AP.CEPID

Abstract

Photodynamic therapy (PDT) is the tripartite process that utilizes light, oxygen and photosensitizers, to produce reactive oxygen species (ROS) that can kill target cells. The main issues associated with conventional PDT are low selectivity, low levels of 1O2 production, dark toxicity and self-aggregation of photosensitizer. Photoimmunotherapy (PIT) is a novel type of molecular targeted therapy, which allows the selective destruction of targets (cancer cells or infected cells) without any damage to normal tissues. In our previous study, we utilized HIV monoclonal antibodies conjugated with toxins for targeting HIV envelope (gp120 and gp41) expressing on the HIV-infected T cells. We demonstrated the immunotoxins kill effectively and specifically targeted cells. However, some restrictions such as immunogenicity and rapid clearance of Ab-drug conjugates, make us to develop HIV immunotherapy (IT) through combination with conventional PDT. We assume this combination, that is so-called PIT, may bypass the issues of either IT or PDT. This tempts us to apply PIT for targeting HIV-infected T lymphocytes expressing HIV envelope on the surface. Therefore, we propose the conjugation of HIV MAbs (anti-gp120 and anti-gp41) with porphyrin-azide. We need to characterize the conjugations (MAb-porphyrin), biochemically and immunologically, including electrophoresis, ELISA, flow cytometry and cytotoxicity assay on HIV-transfected 293T cells. Moreover, we will use confocal and lifetime imaging (FLIM) microscopy to understand internalization and subcellular localization of conjugates and indirectly characterize ROS production. This proposal will be carried out within an ongoing FAPESP/CEPID (Center of Reserarch in Optics and Phothonic, CEPOF) and has a strong support from our partners in USA and UK, and from NIH AIDS REAGENT.

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)

SADRAEIAN, MOHAMMAD; BAHOU, CALISE; DA CRUZ, EDGAR FERREIRA; RAMOS JANINI, LUIZ MARIO; DIAZ, RICARDO SOBHIE; BOYLE, ROSS W.; CHUDASAMA, VIJAY; GONTIJO GUIMARAES, FRANCISCO EDUARDO. Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 23, DEC 2020. (13/07276-1, 17/10910-5, 09/54035-4)

PRATES-SYED, WASIM A.; CHAVES, LORENA C. S.; CREMA, KARIN P.; VUITIKA, LARISSA; LIRA, ALINE; CORTES, NELSON; KERSTEN, VICTOR; GUIMARAES, FRANCISCO E. G.; SADRAEIAN, MOHAMMAD; BARROSO DA SILVA, FERNANDO L.; et al. LP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variant. VACCINES, v. 9, n. 12, DEC 2021. (20/05146-7, 20/07158-2, 17/10910-5, 19/14526-0)

SADRAEIAN, MOHAMMAD; PINTO JUNIOR, FABIO FRANCISCO; MIRANDA, MARCELA; GALINSKAS, JULIANA; FERNANDES, RAFAELA SACHETTO; DA CRUZ, EDGAR FERREIRA; FU, LIBING; ZHANG, LE; DIAZ, RICARDO SOBHIE; CABRAL-MIRANDA, GUSTAVO; et al. Study of Viral Photoinactivation by UV-C Light and Photosensitizer Using a Pseudotyped Model. PHARMACEUTICS, v. 14, n. 3, p. 15-pg., 2022-03-01. (17/10910-5, 13/07276-1, 19/14526-0, 20/05146-7)