PHOTODYNAMIC THERAPY OF SQUAMOUS-CELL CARCINOMA - AN EVALUATION OF A NEW PHOTOSENSITIZING AGENT, BENZOPORPHYRIN DERIVATIVE AND NEW PHOTOIMMUNOCONJUGATE

Photodynamic therapy for cancer depends on the relatively selective di stribution of photosensitizing agents to malignant as compared with no rmal 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 photo sensitizing agent, benzoporphyrin derivative (BPD), to the standard ag ent 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 photod ynamic therapy with either photofrin II, BPD, or a tumour-specific ant i-epidermal growth factor receptor-BPD conjugate. Control groups of li ght alone, anti-EGFr, tumour non-specific MoAb, and tumour non-specifi c 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 St udent's t-tests and linear regression while non-parametric analysis wa s undertaken using Fisher's exact test. Animals receiving BPD alone de monstrated tumour-to-tissue levels of approximately 2:1 while animals receiving the tumour-specific anti-EGFr-BPD conjugate had significantl y better tumour:tissue ratios of 26:1 (P < 0.005). Animals treated wit h 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 t reated 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 w as not statistically different from the group treated with BPD alone. Benzoporphyrin appears to be a more effective photosensitizing agent t han Photofrin II and its tumour selectivity can be improved using a tu mour specific monoclonal antibody conjugate.