Monoclonal antibody-porphyrin conjugate for head and neck cancer: the possible magic bullet.
Although photodynamic therapy in the treatment of large head and neck cancers showed some initial promise, the results in the final analysis have been somewhat disappointing. Lack of specificity and nonhomogeneous uptake of the porphyrin by the tumor are only some of the problems. The conjugation of a monoclonal antibody (UCD/AB 6.01) with hematoporphyrin derivative that preferentially binds to tumor cells offers promise as a therapeutic agent that will not only improve specificity, but vastly enhances tumor cell kill when exposed to light in its photodynamic range. The application of the monoclonal antibody-hematoporphyrin conjugate (AB:HPD) to A-431 squamous cell carcinoma cells in vitro, followed by exposure to light in the 630 nm range, increases the kill ratio by a factor of 10(5) times. The active tumor cell binding site on the cell surface has been found to be on the microvilli, a site at which a 52 kDa protein that is very similar to keratin 8 is found. The clearance of the conjugate from nude mice who have grown an A-431 tumor shows a retention of AB:HPD of approximately 15% and less than 1% in skin and internal organs when measured at 48 hours. Direct application of AB:HPD to fresh pathology specimens containing human squamous cell carcinomas shows binding exclusively limited to the tumor.
Donald
P J
PJ
Department of Otolaryngology-Head and Neck Surgery, University of California, Davis.
Cardiff
R D
RD
He
D E
DE
Kendall
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D002478:Cells, Cultured; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006415:Hematoporphyrins / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D053685:Laser Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis
D000911:Antibodies, Monoclonal; D006415:Hematoporphyrins; D000922:Immunotoxins