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Production and characterization of novel Photoimmunoconjugates for HIV Photoimmunotherapy

Grant number: 17/10910-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2017
Effective date (End): November 30, 2020
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Francisco Eduardo Gontijo Guimaraes
Grantee:Mohammad Sadraeian
Home 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.