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In vitro model of photodynamic therapy using IL-2-photosensitizer conjugate directed to IL-2 receptor-bearing T-cells

Posted on:2001-06-13Degree:Ph.DType:Dissertation
University:Texas A&M UniversityCandidate:Linares, RobertoFull Text:PDF
GTID:1464390014454837Subject:Engineering
Abstract/Summary:
T-cell activation is an essential process for the generation of both humoral and cell-mediated immune response. The recognition of antigens by the resting T-cells on the antigen-presenting cells leads to T-cell activation. Upon their activation, T-cells express the interleukin 2 receptor (IL-2R) and secrete interleukin 2 (IL-2), an essential growth factor for T-cell autocrine growth. A molecular level understanding of the process of T-cell autocrine growth is necessary for the development of novel therapies to treat immune related diseases. For this propose, a mathematical model of this autocrine system was constructed to describe cell secretion, diffusion of ligands, the reaction rate of a ligand with its receptor and the rate of deactivation of a ligand in the medium.;Photodynamic therapy (PDT) has been used to destroy cancerous cells. PDT uses light activated photosensitizers to produce singlet oxygen that causes photodestruction of targeted cells. However, photosensitizers are not highly selective for cancerous cells, causing damage to healthy tissue that is irradiated during the procedure. In order to increase selectivity, monoclonal antibodies have been used to deliver photosensitizers to target cells such as leukemia cells. We have proposed to target IL-2 receptor bearing cells using interleukin 2 photosensitizer conjugates. We have synthesized IL-2-photosensitizer conjugates using the carbodiimide chemistry. Experiments with IL-2-hematoporphyrin (IL-2-HP) and IL-2-chlorin-e6 (IL-2-c6) conjugates were conducted to examine the feasibility of specifically destroying cancerous T-cells.;Leukemia cells were treated with the immuno-conjugate for different periods of time. After incubation, light from a He:Ne laser was applied to treated cells. Cell viability was determined using an MTT assay. The loss of cell viability was increased with longer periods of incubation with the conjugate, and with longer exposure to light. The experimental results show the potential of photodynamic therapy to treat diseases via the IL-2 receptor using IL-2 photoconjugates. This research could lead to improvements in the treatment of autoimmune diseases, leukemia and lymphoma.
Keywords/Search Tags:IL-2, Using, Cells, Receptor, Photodynamic therapy, T-cell
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