CONTROL OF HYPERTROPHIC SCAR GROWTH USING ANTIBODY-TARGETED PHOTOLYSIS

Hypertrophic scar is marked by excess collagen accumulation secondary to an increased vascularization response in the scar and an increase i n fibroblast cell density. It is currently the most debilitating longt erm complication of the surviving burn patient, and at present, there is no routinely effective form of therapy. In this study, we investiga ted the potential use of antibody-targeted photolysis (ATPL) in treati ng hypertrophic scars. An immunoconjugate consisting of a photosensiti zer (Sn-chlorin e6) linked to a monoclonal antibody that binds to huma n myofibroblasts (PR2D3) was prepared, which in response to photoactiv ation produces singlet oxygen in close proximity to the target cell su rface. The model used for these studies consisted of 1-mm(3) human hyp ertrophic scar tissue implants in athymic mice, These implants increas e approximately 20-fold in volume over a period of 15 days. Four days after implantation immunoconjugate was injected directly into scar imp lants and allowed to diffuse throughout for 24 hr before implants were illuminated with laser light at 630 nm (120 J/cm(2)), ATPL treatment caused a significant reduction in total growth compared to the untreat ed controls (P < 0.05). No effect was observed when an irrelevant conj ugate (anti-Pseudomonas aeruginosa) was used. Histological examination of the ATPL-treated implants 24 hr post-ATPL revealed the presence of a large number of lipid droplets indicative of massive cell damage an d infiltration by mononuclear cells and neutrophils. (C) 1996 Academic Press, Inc.