Targeting a neoantigen derived from a common TP53 mutation sciencemag.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from sciencemag.org Daily Mail and Mail on Sunday newspapers.
Akoya and Johns Hopkins’ collaborative agreement supports pioneering new approach to immunotherapy biomarker discovery and validation
Industry News: Akoya and Johns Hopkins’ collaborative agreement supports pioneering new approach to immunotherapy biomarker discovery and validation
For the first time Astronomy and Pathology (AstroPath™) come together to discover and clinically validate new spatial phenotypic signatures using multiplex immunofluorescence
03 Mar 2021
®, has announced a collaboration with the Bloomberg-Kimmel Institute for Cancer Immunotherapy (BKI) and the Bloomberg Center for Physics and Astronomy at the Johns Hopkins University School of Medicine.
The agreement brings together Akoya’s Phenoptics™ multiplex immunofluorescence (mIF) platform for spatial phenotyping and Johns Hopkins’ AstroPath™ platform, an interdisciplinary team of immunologists, pathologists, oncologists, and astrophysicists focused on immuno-oncology biomarker discovery and val
Researchers develop mutant gene-targeted immunotherapy approach to fight cancers
A novel targeted immunotherapy approach developed by researchers at the Ludwig Center, the Lustgarten Laboratory, and Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center employs new antibodies against genetically altered proteins to target cancers.
The researchers targeted their immunotherapy approach to alterations in the common cancer-related p53 tumor suppressor gene, the RAS tumor-promoting oncogene or T-cell receptor genes. They also tested the therapy on cancer cells in the laboratory and in animal tumor models. Their findings are reported in three related studies published March 1 in
Science Immunology,
Diabodies see the unseeable
RAS oncogene mutations are common in various cancers, controlling their growth and survival. Targeting mutant RAS proteins with antibodies has been unsuccessful due to low surface expression, even when targeting mutant RAS peptides presented via HLA on the surface of cancer cells. Douglass
et al. used phage display to generate single-chain variable fragments (scFvs) specific for mutant RAS peptide-HLA complexes. The authors tested various bispecific, T cell–engaging antibody formulations, finding that single-chain diabodies (scDbs) combining the aforementioned scFv with an anti-CD3 scFv were able to induce T cell activation and subsequent killing of tumor cells expressing mutant RAS peptide-HLA complexes. This scDb approach opens the door for antibody-based therapies against mutant neoantigens expressed at very low levels on the surface of cancer cells.
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