Many aggressive human breast cancers overexpress Her2/neu, an epidermal growth f
ID: 54454 • Letter: M
Question
Many aggressive human breast cancers overexpress Her2/neu, an epidermal growth factor receptor surface protein which drives cell proliferation. Herceptin. a monodonal antibody which recognizes Her2. is used to treat such cancers. Monoclonal antibodies are expensive to manufacture and must be administered intravenously. Several biotech firms are trying to devise 'cancer vaccines' which could provoke the patient to make her own immune response against Her2. The approach is different in another way: these vaccines attempt to provoke the generation of Cytotoxic T-Lymphocytes (rather than antibodies), which will attack the cancer cells. The challenge is that Her2 is a 'self protein - you are ordinarily tolerant to it and won't respond to it. However, it is possible to 'break tolerance* by administering a self-antigen with a powerful adjuvant Neuvax. one such experimental vaccine, links a nonapeptide from Her 2 (the nona pep tide is a potential T-Cell epitope) to a powerful immunoadjuvant Neuvax has shown promising results in early clinical trials. but it worKS only for women with certain genetic backgrounds What might be the genetic difference between those for whom it works, and those for whom it doesn't?Explanation / Answer
The difference lies in the HLA proteins coded by the MHC-I gene locus. The gene loci HLA-A, HLA-B, and HLA-C code Class 1 MHC proteins, which are expressed on all nucleated cells. Due to the allelic variations, different alleles code different proteins that vary in their ability to bind antigenic peptides and their affinity to bind to the antigenic peptides.
* People who bare HLA class I alleles which encode proteins that bind to the antigen strongly and present them to Tc cells mount an immune response against the antigens.
* On the othe hand, people who have allles which encode proteins that do not bind to the antigenic fragments cannot mount an immune response, and hence are non-responsive to the antigen.
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