Targeted gene therapy using anti-pl85HER2 immunoliposomes
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: This application proposes to develop anti-p185HER2 immunoliposomes containing genes as a novel strategy to treat advanced breast cancer. There are 3 key components to this new strategy. The first component are liposomes, small particles of fat that are hollow and can be used to carry potent anti-cancer drugs such as chemotherapy. The second component are genes, which are made up of DNA and carry instructions to cells. The idea that genes can be given to patients as a form of treatment is called gene therapy or gene medicine. Since many cancers, such as breast cancer, involve defective or abnormal genes that have sprung up in cancer cells, it is possible to imagine correcting cancer or causing cancer cells to die by putting new genes into the cells. However, although genes can be put into cells in the test tube, scientists have not yet developed a practical and effective way to put genes back into breast cells in patients. Liposomes can be used to carry genes. However, the liposomes will not necessarily be able to find the tumor cells in the body so as to deliver the genes. Antibodies, the third component of this strategy, are proteins produced by the immune system to fight invaders such as bacteria, viruses, and cancer cells. Antibodies can recognize different parts of these invaders with precision. A single antibody type that recognizes a single target, such as a part of a cancer cell, is called a monoclonal antibody, and can be produced in the laboratory. When antibodies are linked to liposomes, the resulting particles are called immunoliposomes (ILs). ILs can use their antibody part to recognize cancer cells. ILs can be made that recognize a target called p185HER2, a cancer protein produced by the HER2 oncogene. This protein molecule plays a carefully regulated role in the growth and development of certain normal cells. However, in many patients with breast cancer, the breast cancer cells contain many times more copies of the p185HER2 protein than normal, which helps the cancer to form in the first place and to grow rapidly. We have developed different versions of anti-p185HER2 ILs (liposomes containing an antibody that recognizes and targets breast cancer cells with high levels of p185HER2). We can use anti-p185HER2 to target breast cancer cells and deliver to them high concentrations of effective chemotherapy drugs. This should result in enhanced killing of cancer cells as well as diminished side effects due to exposure of normal cells and tissues to chemotherapy. For this reason, these ILs have been likened to "smart bombs" in their ability to selectively find and hit cancer cells, while avoiding normal cells.
 
 
 
 
 
 
 
 This application proposes to develop anti-p185HER2 ILs capable of carrying genes to breast cancer cells. First, a test gene will be used to determine the best procedure or recipe for making the ILs. Tests in test tubes and in mice will be done to determine the ability of different versions of Ils to recognize cancer cells and deliver the gene to them. Next, using what appear to be the best recipes, ILs containing a gene called HSVtk will be prepared. This gene can activate an ordinarily harmless drug called ganciclovir (GCV), turning it into a lethal drug. Thus, cancer cells targeted by ILs will get the HSVtk and become susceptible to killing by GCV. ILs will be tested for their ability to deliver the HSVtk gene in test tubes and in mice, and to cause their death when exposed to GCV. If this strategy is successful, it may mean that anti-p185HER2 ILs can be used to deliver other cancer-fighting genes to breast cancer cells as well.