Photodynamic therapy and the immune system in experimental oncology.

Abstract

Photodynamic therapy (PDT), a newly established treatment for solid tumors, involves the systemic administration of a tumor localizing photosensitizer that is only activated when exposed to light of appropriate wavelength. Photoactivation of the photosensitizer in the presence of oxygen results in the generation of highly cytotoxic molecular species. The PDTmediated antitumor effect is oxygen dependent and is the consequence of direct cytotoxicity and an antivascular effect which impairs blood supply to the area. Furthermore, the development of a generalised inflammatory state in the treatment region and immunological mechanism may contribute to tumor regression. The most widely studied PDT drugs both in experimental and clinical trials have been hematoporphyrin derivative and Photofrin (a complex mixture of monomeric and oligomeric porphyrins). While encouraging results have been obtained with these drugs, their documented limitations have led to the search for second generation photosensitizers in the hope of increasing the efficacy of the treatment (clearly definable molecular structure, activation at longer, more penetrating wavelengths of light and a more rapid clearance from the subject). Second generation photosensitizers that are currently under clinical evaluation include tin etiopurpurin dichloride (SnET2), lutetium texaphyrin, meso-tetrahydroxyphenylchlorin (m-THPC), phthalocyanines and benzoporphyrin derivatives, monoacid ring A (BPD-MA, Verteporfin) and ALA (5-aminolevulinic acid).