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Photodynamic therapy of squamous cell carcinoma : an evaluation of a new photosensitizing agent and photoimmunoconjugate

University of British Columbia

Photodynamic therapy for cancer depends on the relatively selective distribution of photosensitizing agents to malignant as compared to normal tissues, rendering the malignant cells more susceptable 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 tumor specific monoclonal antibody - BPD conjugate to improve the tumor localizing properties of BPD. Treatment consisted of photodynamic therapy with either Photofrin II, BPD, or a tumor specific antiepidermal growth factor receptor -BPD conjugate. Control groups of light alone, antiEGFr, tumor non-specific antiCEA, and tumor nonspecific antiCEA-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 tumor and to normal mucosa was undertaken using a spectrophotometric assay. Parametric statistical analysis included student "t" tests and linear regression while non-parametric analysis was undertaken using Fisher's exact test. Animals receiving BPD alone demonstrated tumor to tissue levels of approximately 2:1 while animals receiving the tumor specific antiEGFr-BPD conjugate had significantly better tumor:tissue ratios of 26:1. (p < 0.005) Animals treated with Photofrin II had a one 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 tumor specific antiEGFr-BPD conjugate at a twentieth the total dose of BPD had an 80% one 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 tumor selectivity can be improved using a tumor specific monoclonal antibody conjugate.

Thesis/Dissertation

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2008-08-13

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http://hdl.handle.net/2429/1378

Surgery

University of British Columbia

UBCV

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