Targeting Critical Cells of the Immune System

Recently, much effort has been placed on harnessing the power of the patient’s immune system to recognize and destroy tumor cells, in the same fashion that the immune system neutralizes infectious pathogens. As vaccination has been used as a potent and cost effective method to block the spread and severity of infectious disease, it is hoped that vaccination against tumor antigens will provide a similar success in the fight against cancer.

In order to facilitate the development of effective cancer vaccines, my laboratory is focusing on strategies to deliver antigens to specialized antigen presenting cells of the immune system. Towards this goal, we have isolated peptidic ligands that mediate specific uptake by immunopotent dendritic cells (DCs). The peptide is functional outside the context of the phage and is able to deliver a nanoparticle to DCs in vitro. Although selected on cells in vitro, the peptide is able to direct antigens and genes to DCs in vivo. Liposomes bearing the DC targeting peptide are able to deliver a transcriptionally active gene to DCs in a mouse model.

Furthermore, we demonstrate that a low-dose injection into mice of phage bearing the DC-targeting peptide yields faster and higher immune responses against phage-associated antigens than control-phage injections. Furthermore, we have identified ligands for other cells of the immune system that may also play a role in the development of an immune response. With these reagents in hand, we are using these immune cell targeting ligands to deliver antigens and immunomodulating compounds in a cell-specific fashion in order to develop effective cancer vaccines. These studies will serve as a pathway to performing human trials later. Our objectives are to:

  • Utilize immune cell-targeting ligands as delivery reagents for generating immune responses to antigens administered by genetic and synthetic peptide vaccines in order to create prophylactic and therapeutic cancer vaccines.
  • Obtain ligands for regulatory T cells that play a key role in determining the response to an antigen by discriminating between self and non-self. We will utilize these ligands to deliver immunoregulating agents specifically to this population of T cells.

More information about this project can be found in the following publication:

McGuire, Michael J.; Sykes, Kathryn F.; Samli, Kausar N.; Timares, Laura; Barry, Michael A.; Stemke-Hale, Katherine; Tagliaferri, Frank; Logan, Mark; Jansa, Kimberly; Takashima, Akira; Brown, Kathlynn C.; Johnston, Stephen Albert (2004) "A Library-Selected, Langerhans Cell-Targeting Peptide Enhances an Immune Response" DNA and Cell Biol. 23, 742-752.