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This news release, issued by Johns Hopkins Medicine, describes a novel targeted immunotherapy approach. This new approach employs bispecific antibodies to treat cancer by eliciting a Tcell response against mutated p53. The researchers used the Highly Automated Macromolecular Crystallography (AMX) and Frontier Microfocusing Macromolecular Crystallography (FMX) beamlines to characterize the molecular structure of the proteins. AMX and FMX are beamlines at the National Synchrotron Light Source II (NSLS-II) a U.S. Department of Energy (DOE) Office of Science User Facility at Brookhaven National Laboratory. NSLS-II offers a comprehensive suite of life science research capabilities. Johns Hopkins media contacts: Amy Mone, 410-614-2915, amone@jhmi.edu, or Valerie Mehl, 410-614-2916, mehlva@jhmi.edu. Brookhaven Lab media contacts: Cara Laasch, 631-344-8458, laasch@bnl.gov or Peter Genzer, 631-344-3174, genzer@bnl.gov.
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IMAGE: Novel cancer immunotherapy approach inverts a missing gene copy into an immune cell-activating signal. view more
Credit: Elizabeth Cook
Researchers developed a prototype for a new cancer immunotherapy that uses engineered T cells to target a genetic alteration common among all cancers. The approach, which stimulates an immune response against cells that are missing one gene copy, called loss of heterozygosity (LOH), was developed by researchers at the Ludwig Center, Lustgarten Laboratory and the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center.
Genes have two alleles, or copies, with one copy inherited from each parent. Cancer-related genetic alterations commonly involve the loss of one of these gene copies.
Novel immunotherapy approach targets cancers
Appeared in BioNews 1086
Designer antibodies can alert the immune system to cancerous proteins, slowing tumour growth in mice – three independent studies demonstrate.
Researchers at the John Hopkins University School of Medicine, Maryland, investigated the notorious cancer proteins, p53 and RAS. Mutations in p53 and RAS are common among cancers, however, drug therapies have been largely unsuccessful. Therefore, researchers aimed to develop specific antibodies, like those of our immune system, to target these proteins instead. Antibodies detect precise protein fragments, called peptides. These peptides can be presented on the cell surface when complexed with the human leukocyte antigen (HLA) proteins, said Dr Katharine Wright, lead author of one of the studies. HLA proteins present peptides to immune cells called T cells. These mutant peptide-HLA complexes serve as antigens and mark cancer cells as foreign to the immune system.
Two of the three research studies led by Jacqueline Douglass, M.D., Ph.D. candidate at the Johns Hopkins University School of Medicine and Emily Han-Chung Hsiue, M.D., Ph.D., postdoctoral fellow at Johns Hopkins report on a precision medicine immunotherapy approach that specifically kills cancer cells by targeting mutant protein fragments presented as antigens on the cancer cell surface.
Although common across cancer types, p53 mutations have not been successfully targeted with drugs. Genetic alterations in tumor suppressor genes often resulted in their functional inactivation. Traditional drugs are aimed at inhibiting proteins. Inhibiting an already inactivated tumor suppressor gene protein in cancer cells, therefore, is not a feasible approach, says Hsiue, lead author on the