Photo Immuno-Resetting Therapy (PIRT) of cancer involves the systemic administration of a tumor-localizing agent that is only toxic when irradiated by light of the appropriate wavelength (photosensitizer). Because tumor destruction requires the geometric presence of the photosensitizer and light, each of which are non-toxic, it is possible to elicit tumor site-specific killing without damage to surrounding tissues. Although the theoretical basis and therapeutic benefit implications of this treatment modality are extremely attractive, in practice, PDT to date has not translated into a broad-based successful treatment of neoplastic disease. We have substantially improved the efficacy of PDT by synthesizing new agents that uniquely meet multiple criteria for an effective PDT photosensitizer for the treatment of cancer including:
- Direct tumor cell killing versus vascular damage
- High uptake into tumor tissue
- High discrimination ratio of retention between tumor and normal tissue
- High efficiency of light absorption in the therapeutic window
- No photosensitization of skin
- Low systemic toxicity
- High Therapeutic Index
- Strong post-PIRT immunization against tumor
Preclinical testing with these agents has demonstrated their ability to destroy large tumor masses beyond the range of light penetration and to elicit anti-tumor immunity. We are pursuing the further development of our lead candidates for clinical testing.
