Her2/neu is over-expressed in various types of tumor cells, including 20-30% of breast cancers, adenocarcinomas of the ovary, salivary gland, stomach and kidney, colon cancer, and non-small cell lung cancer. Passive immunotherapeutics like Herceptin control and prevent further tumor cell growth. Unlike active immunotherapeutics, Herceptin does not mediate the immunological cellular destruction.
Active immunotherapeutics such as vaccines elicit T helper-1 (Th1) and Cytotoxic T lymphocytes (CTL) biased immune responses and are generally observed for proteins expressed in the intracellular compartment, and less prominently with extracellular or secreted proteins. Rapid degradation of a protein containing polyepitopes can contribute to establishing a bias in the immune response, facilitate antigen presentation and, perhaps assist in establishing specificity of the immune response. This type of immunological response should result in immunological cellular destruction.
University of California, Irvine researchers have developed a recombinant polynucleotide encoding Her2/neu target antigen. This recombinant polynucleotide contains two regions of the human Her2/neu molecule which demonstrated the lowest degree of homology with other known normal human proteins as the putative target antigen sequence for a genetic vaccination strategy. This target sequence was chosen to minimize any potential cross reactive auto-immune response and to maximize specificity of the elicited immune response. These portions of human Her2/neu contain some of the previously identified T cell epitopes. Because this sequence is predominantly intracellular and represents a truncated or partial protein sequence, the protein is anticipated to be rapidly degraded and presented in the context of MHC class I and thus be available for CTL recognition.
|United States Of America||Issued Patent||7,446,185||11/04/2008||2001-288|