Developing Better Vaccines
Pascal’s CD74 program consists of technologies discovered at The University of British Columbia (UBC) that relates to the role CD74, a chaperone protein, plays in the presentation of not only Major Histocompatibility Complex Class II (MHC-II) molecules in dendritic cells, but also in the presentation of MHC-I molecules. The discovery of CD74’s involvement in the presentation of MHC-I is ground-breaking and may lead to greatly improved immune responses to pathogen or cancer antigens through the activation of dendritic cells with vaccine adjuvants.
Dendritic cells are immune system cells that present antigens on their surfaces that are recognized by the immune system’s T cells, which in turn cause the destruction of the cells when the presented antigens are from foreign proteins. In dendritic cells, both MHC-1 and MHC-II molecules are responsible for the presentation of antigens on the cells’ surfaces. MHC molecules are formed in the endoplasmic reticulum and are then transported through complex structures where the antigens are processed and “loaded” into the MHC molecules, which then transport the antigens to the cells’ surfaces.
The discovery that CD74 plays a role in the presentation of antigens with MHC-I provides Pascal with methods of modulating MHC-I mediated immune responses through the modification of CD74, causing specific antigenic peptides to be presented and transfected in specific cells for expression. This process is essential for CD8+ T cell mediated responses against viruses, tumours, self-antigens and allografts.
Several antigenic molecules such as HIV nef, Influenza M, and ovalbumin have been cloned into CD74 protein. These different DNA constructs have been introduced into a mammalian expression system based on an AdMax™ adenovirus vector system. It is planned to express these constructs in cells such as dendritic cells and to measure and characterize the T and B cell responses induced by these different recombinant viral constructs after infection of mice in-vivo.
A CD74-dependent MHC class I endolysosomal cross-presentation pathway. Basha G, Omilusik K, Chavez-Steenbock A, Reinicke AT, Lack N, Choi KB, Jefferies WA. Nat Immunol. 2012 Feb 5;13(3):237-45.