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 in fibroblast cell density. It is currently the most debilitating long-term complication of the surviving burn patient, and at present, there is no routinely effective form of therapy. In this study, we investigated the potential use of antibody-targeted photolysis (ATPL) in treating hypertrophic scars. An immunoconjugate consisting of a photosensitizer (Sn-chlorin e6) linked to a monoclonal antibody that binds to human myofibroblasts (PR2D3) was prepared, which in response to photoactivation produces singlet oxygen in close proximity to the target cell surface. The model used for these studies consisted of 1-mm 3 human hypertrophic scar tissue implants in athymic mice. These implants increase approximately 20-fold in volume over a period of 15 days. Four days after implantation immunoconjugate was injected directly into scar implants 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 untreated controls (P < 0.05). No effect was observed when an irrelevant conjugate (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 and infiltration by mononuclear cells and neutrophils.
Wolfort
S F
SF
Surgical Services, Massachusetts General Hospital, Boston, 02114, USA.
Reiken
S R
SR
Berthiaume
F
F
Tompkins
R G
RG
Yarmush
M L
ML
D000818:Animals; D000911:Antibodies, Monoclonal; D002735:Chlorophyllides; D017439:Cicatrix, Hypertrophic / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D010782:Photolysis; D011166:Porphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014617:Vacuoles / Q000473:pathology
D000911:Antibodies, Monoclonal; D002735:Chlorophyllides; D000922:Immunotoxins; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C062985:phytochlorin