Delivering DNA Vaccine by Transdermal Electroporation
Abstract
The HLA-A2 binding peptide, KIFGSLAFL, derived from breast cancer associated antigen HER-2/neu, is to be delivered transdermally by electroporation to the dermal Langerhans cells (LC), to stimulate the cytotoxic T-lymphocyte (CTL) response to breast cancer cells. We have extended, by using anionic lipids, the upper molecular weight limit of transdermal delivery of macromolecules by electroporation to <10,000. This enables the delivery of antigenic peptides but not minigenes. We measured the transdermal flux of antigenic peptides (M.W.^9,000) to be in the order of 1-10 mug/cm2/min, when 1 msec pulses of lOOV were applied to the skin at 1 Hz. The KlFGSLAFL peptide was delivered to HLA-A2/Kb transgenic mice as a vaccine by transdermal electroporation. CTL response to delivery of the peptide vaccine KIFGSLAFL has so far been negative. We attribute the lack of response to either that the peptide delivered was insufficient, or that the adjuvants in transdermal electroporation were absent because of molecular weight limitation. Increase the amount of delivery, with or without co-injection of adjuvant, could overcome the problem.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA409785
Entities
People
- Sek-wen Hui
Organizations
- Health Research, Incorporated