Our laboratory has continued investigation of photodynamic therapy for the treatment of malignancy. We have shown that conjugation of monoclonal antibody to a weak sensitizer will improve the specificity as well as the long-term cures in an in vivo model of photodynamic therapy. We continue with investigations in human trials to establish the maximum tolerated dose of phototherapy for intrapleural delivery. As of June of 1992 42 patients have been entered on an intrapleural photodynamic therapy trial with light dose escalation in cohorts of three patients. We have published the ability to monitor the light through these treatments. We have shown that the maximum tolerated dose of intraoperative pleural photodynamic therapy is 30 Joules/cm-squared of light after a 24 hour dosing of 2 mg/kg of Photofrin II. We found the next highest dose of phototherapy light (32.5 Joules/cm-squared) resulted in esophageal complications. We have also investigated use of a number of novel compounds to prevent tumor necrosis factor toxicity. Potassium channel activator, Nicorandil, was found to decrease macrophage TNF production from an LPS challenge possibly through a reduction in respiratory burst. Moreover, the nitron PBN was found to abrogate the lethality of LPS in vivo through down regulation of serum production of tumor necrosis factor. Investigations of other compounds which may be useful in protecting against cytokine toxicity is continuing in our section within in vitro and in vivo models.
