A comparison of direct and liposomal antibody conjugates of sulfonated aluminum phthalocyanines for selective photoimmunotherapy of human bladder carcinoma.
There is a need to improve the selectivity of photodynamic therapy and for better targeting of tumor cells within specific tumor compartments. Selective in vitro phototoxicity of a human bladder carcinoma cell line 647V has been achieved by targeting sulfonated aluminum phthalocyanines (AlSPc) with monoclonal antibodies. Aluminum tetra-3 sulfonyl chloride phthalocyanine (PC) or rhodamine sulfonyl chloride were directly coupled to antibodies by a sulfonamide linkage and AlSPc or carboxyfluorescein were encapsulated in liposomes of the small unilamellar vesicle type (SUV) bearing antibody. Antibody E7 (IgM subclass), which recognized an antigenic determinant expressed on 647V but was absent on T24 a control human bladder carcinoma cell line, and a control IgM antibody were used. The effects of the two types of conjugate were compared. Immunofluorescence studies on living cells demonstrated specific cell surface localization of conjugates at 4 degrees C and internalization at 37 degrees C. Phototoxicity was measured by 3-(4,5-dimethylthiazol-2-5-diphenyltetrazolium) bromide assay after exposing AlSPc-sensitized cells to red light. Significant AlSPc dose-dependent phototoxicity of the order 4 degrees C < 4 degrees C plus 37 degrees C < 37 degrees C was observed with E7-SUV and E7-PC in the range 1-8 microM AlSPc. At equimolar AlSPc doses absolute toxicity was similar for the two conjugate types, but at equimolar antibody doses, the liposomal conjugate was more effective by up to 13-fold. Addition of urine during illumination decreased toxicity, which was attributed to the presence of protective elements. The results suggest that photosensitizers such as AlSPc could be used for antibody-directed therapy and in particular for selectively damaging tumor cells of the epithelial cell compartment in bladder carcinoma by intrabladder administration. The therapeutic ratio, which takes into account both specific and nonspecific toxicity, was greater for the liposome conjugate than for the direct conjugate indicating their greater suitability for in vivo instillation.
Morgan
J
J
Centre de Recherches Chirurgicales, Creteil, France.
Lottman
H
H
Abbou
C C
CC
Chopin
D K
DK
D000535:Aluminum / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007167:Immunotherapy; D007211:Indoles / Q000276:immunology / Q000627:therapeutic use*; D008081:Liposomes; D009942:Organometallic Compounds / Q000276:immunology / Q000627:therapeutic use*; D010789:Phototherapy / Q000009:adverse effects; D013451:Sulfonic Acids / Q000737:chemistry; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D018796:Immunoconjugates; D007211:Indoles; D008081:Liposomes; D009942:Organometallic Compounds; D013451:Sulfonic Acids; C060570:aluminum phthalocyanine; D000535:Aluminum