A method of identifying a ligand as a candidate for incorporation into a pharmaceutical composition that modulates antigen presenting cell activity

Available for licensing and commercial development are novel biotechnological tools, prophylactics, therapeutics, and methods for modulating the activation state of an antigen presenting cell (APC) and thereby modulating the activation of a killer T cell. The activation of a killer T cell can occur in a two cell complex and two sequential steps: a) in the first step, an APC stimulates a T helper T cell, which in turn stimulates or "superactivates" the APC to differentiate to a state where it can independently stimulate a killer T cell; b) in the second step, the APC encounters the killer T cell and stimulates it so that killer T cell priming is achieved in a helper independent fashion. The first step can be bypassed altogether by viral infection or an interaction with certain molecules at the cell surface of APCs, such as CD40. More specifically, the invention consists of a method of identifying a ligand as a candidate for incorporation into a pharmaceutical composition, such as a therapeutic or prophylactic product, that modulates antigen presenting cell activity, comprising contacting an APC with a candidate ligand which interacts with the APC, analyzing the activation state of the APC; and selecting ligands that activate a killer T cell in the absence of a helper T cells as the candidates for incorporation into the pharmaceutical. Also claimed are related methods where the ligand interacts with CD40 or where the APC is a dendritic cell. The embodiments have several applications in the field of immunology, and enable to manufacture novel pharmaceuticals and vaccine components for the treatment and prevention of cancer, systemic infection, and autoimmune responses. Publication: JP Ridge, F Di Rosa, and P Matzinger, "A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell," Nature 1998 Jun 4; 393 (6684):474-8.

U.S. Patent No. 6,680,176 issued 20 Jan 2004 (HHS Reference No. E-055-1999/0-US-01) Inventors: Polly Matzinger, John P. Ridge (NIAID)

Licensees sought. In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.