title: Photodynamic therapy of squamous cell carcinoma. An evaluation of a new photosensitizing agent, benzoporphyrin derivative and new photoimmunoconjugate.
abstract: Photodynamic therapy for cancer depends on the relatively selective distribution of photosensitizing agents to malignant as compared with normal tissues, rendering the malignant cells more susceptible to light-mediated damage. Photodynamic therapy has been used with only moderate success to date. The purpose of this study was to compare a new photosensitizing agent, benzoporphyrin derivative (BPD), to the standard agent presently in use, photofrin II, in a hamster cheek pouch model of squamous cell carcinoma. As well we have investigated the potential of using a tumour-specific monoclonal antibody-BPD conjugate to improve the tumour localizing properties of BPD. Treatment consisted of photodynamic therapy with either photofrin II, BPD, or a tumour-specific anti-epidermal growth factor receptor-BPD conjugate. Control groups of light alone, anti-EGFr, tumour non-specific MoAb, and tumour non-specific MoAb-BPD conjugate were included with the contralateral cheek pouch of each animal acting as a dark control. An assessment of differential delivery of BPD to tumour and to normal mucosa was undertaken using a spectrophotometric assay. Parametric statistical analysis included Student's t-tests and linear regression while non-parametric analysis was undertaken using Fisher's exact test. Animals receiving BPD alone demonstrated tumour-to-tissue levels of approximately 2:1 while animals receiving the tumour-specific anti-EGFr-BPD conjugate had significantly better tumour:tissue ratios of 26:1 (P < 0.005). Animals treated with photofrin II had a 1 month cancer-free survival of 27% while animals treated with BPD had an improved survival of 67% (P = 0.03). The group treated with the tumour-specific anti-EGFr-BPD conjugate at a twentieth the total dose of BPD had an 80% 1 month cancer-free survival which was not statistically different from the group treated with BPD alone. Benzoporphyrin appears to be a more effective photosensitizing agent than Photofrin II and its tumour selectivity can be improved using a tumour specific monoclonal antibody conjugate.
authors.affiliation: Department of Surgery, University of BC, Vancouver, Canada.
authors.forename: A W
authors.initials: AW
authors.lastname: Hemming
authors.forename: N L
authors.initials: NL
authors.lastname: Davis
authors.forename: B
authors.initials: B
authors.lastname: Dubois
authors.forename: N F
authors.initials: NF
authors.lastname: Quenville
authors.forename: R J
authors.initials: RJ
authors.lastname: Finley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology; D002610:Cheek; D006224:Cricetinae; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000276:immunology; D008297:Male; D008647:Mesocricetus; D010778:Photochemotherapy; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C504224:benzoporphyrin D; D017323:Dihematoporphyrin Ether; D066246:ErbB Receptors