Lasers have traditionally been used in medicine as a cautery tool to thermally burn, ablate, or denature biologic tissues on a macroscopic scale. Selective damage on a microscopic scale has generally been limited to situations where the laser can be focussed into a single cell or into transparent organs such as the eye. Techniques for selective laser damage in nontransparent tissues have recently been developed which involve irradiation of endogenous or exogenous chromophores within tissues using an unfocussed laser beam. Laser energy absorbed by the chromophore can either be converted to thermal energy or used to initiate photochemical reactions. The objectives of the proposed research are to characterize and optimize approaches for selective light-induced themal or photochemical damage using chromophores which are bound to, and localized by monoclonal antibodies on the surface of cancer cells. Because the principal endogenous chromophores absorb strongly below 600 nm and water absorbs above 1300 nm, exogenous chromophores which absorb in the """"""""therapeutic window"""""""" (600-1300nm) will be prepared and characterized. For antibody-mediated photolysis, chromophores will be linked to MAbs and MAb frgments directly or via intermediaries. Conjugates will be characterized as to their chromophore substitution ratios, binding characteristics, and photochemical and physiochemical properties. In vitro and in vivo experiments with antibody-bound chromophores will be performed to evaluate the efficacy and exent of thermal or photochemical damage induced by laser irradiation. The technique of antibody-mediated photolysis shows great promise for therapy in situations where tumor masses are accessible to irradiation through the body surface or via optical fibers.
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