Keyhole limpet hemocyanin challenge model for studying adaptive immune system responses in early-phase clinical drug development

Saghari, M.

Autoimmune diseases affect approximately 5–8% of the global population. Current drugs often lack specificity and have many side effects. New treatments based on a better understanding of the underlying cellular and molecular mechanisms are needed. The use of keyhole limpet hemocyanin (KLH), derived from the mollusk species Megathura crenulata, offers the opportunity to characterize immune responses. KLH stimulates both T cells (cellular immune response) and the production of antibodies via B cells (humoral immune response). The cellular immune response can be objectively assessed after a subsequent dermal administration using imaging techniques such as Laser Speckle Contrast Imaging (LSCI) and multispectral imaging. In this dissertation, we used a KLH challenge model to evaluate immune responses in healthy volunteers who were administered investigational compounds KY1005, EDP1066, or EDP1815. KY1005 is an inhibitor of OX40L, which is expressed on various immune cells. The effects...Show moreAutoimmune diseases affect approximately 5–8% of the global population. Current drugs often lack specificity and have many side effects. New treatments based on a better understanding of the underlying cellular and molecular mechanisms are needed. The use of keyhole limpet hemocyanin (KLH), derived from the mollusk species Megathura crenulata, offers the opportunity to characterize immune responses. KLH stimulates both T cells (cellular immune response) and the production of antibodies via B cells (humoral immune response). The cellular immune response can be objectively assessed after a subsequent dermal administration using imaging techniques such as Laser Speckle Contrast Imaging (LSCI) and multispectral imaging. In this dissertation, we used a KLH challenge model to evaluate immune responses in healthy volunteers who were administered investigational compounds KY1005, EDP1066, or EDP1815. KY1005 is an inhibitor of OX40L, which is expressed on various immune cells. The effects of KY1005 on the humoral and cellular immune response via the KLH challenge were evident. However, the two microbial investigational compounds, EDP1066 and EDP1815, showed limited efficacy. These findings highlight the importance of evaluating effects of investigational drugs in early-phase clinical research.
Although the primary objectives of the dissertation were achieved, further characterization of immune mechanisms is necessary.
Show less

Leiden University Scholarly Publications

View statistics

Documents

In Collections

Keyhole limpet hemocyanin challenge model for studying adaptive immune system responses in early-phase clinical drug development

Funding