Method for Identifying Novel Cancer Antigens for Vaccine Development
Dorothee Herlyn, Rajasekharan Somasundaram, and Rolf K. Swoboda
A novel method for cloning MHC class II-dependent antigens from cancer cells has been developed for use in creating new cancer vaccines. Cancer antigens bound to MHC molecules on the surface of specialized antigen presenting cells (APCs) are recognized by CD4+ T-helper (Th) lymphocytes, which play a central role in providing protective immunity against cancer. New MHC class II-dependent cancer antigens therefore have significant promise as vaccine immunogens. They have previously been identified by artificially fusing libraries of cancer peptides with MHC molecules, expressing them in standard cell lines, and screening them for activation of CD4+ Th cells in culture. However, this method fails to recapitulate the complexity of antigen-MHC processing and presentation by APCs; requires prior knowledge of the MHC restriction element used by the Th cell and is very laborious. Wistar scientists have developed a phage method for expressing tumor cDNA libraries directly in APCs, without prior fusion to MHC. The APCs naturally process and present these tumor peptides on their surface, where they can be readily screened for CD4+ Th cell activation. The method has been used at Wistar to identify a novel Th cell antigen that is shared by melanomas and gliomas, and may be useful for the identification of other antigens for cancer vaccine development.
The technology is a new method for identifying and cloning novel cancer antigens. Unlike earlier methods for cloning cancer antigens, this method does not require prior knowledge of which MHC fragments should be used to ensure recognition by Th cells and can be directly used to develop new antigens for cancer vaccines and diagnostics.
This technology is protected by International PCT Application WO 2006/138449 A2, “Method for Identifying a MHC Class II-Dependent Tumor-Associated T Helper Cell Antigen” (Herlyn, D.; Somasundaram, R.; Swoboda, R.; December 28, 2006).
U.S. Patent Application No. 11/917,363 (US-2010-0080792, published 04/01/2010).
Swoboda et al.; 2007. “Shared MHC class II-dependent melanoma ribosomal protein L8 identified by phage display”. Cancer Res 67: 3555-3559