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Bispecific antibodies targeting mutant RAS neoantigens

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. ....

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Mutant gene-targeted immunotherapy approach developed

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 ....

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False Positives a Problem for SNP Chips

After hearing of cases where women had surgery scheduled after wrongly being told they had very rare genetic variations in the gene <i>BRCA1</i> that could significantly increase risk of breast cancer, researchers conducted a large-scale analysis of the technology used. They found that it wrongly identified the presence of very rare genetic variants in the majority of cases. ....

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Tech used to find super rare gene variants 'more likely to be wrong than right'

Tech used to find super rare gene variants 'more likely to be wrong than right'
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Genetic Testing Detects Uncommon Variants Incorrectly

Genetic Testing Detects Uncommon Variants Incorrectly
by Angela Mohan on
February 16, 2021 at 3:03 PM
BMJ.
After hearing of cases where women had surgery scheduled after wrongly being told they had very rare genetic variations in the gene BRCA1 that could significantly increase risk of breast cancer, a team at the University of Exeter conducted a large-scale analysis of the technology using data from nearly 50,000 people. They found that the technology wrongly identified the presence of very rare genetic variants in the majority of cases.
The team analyzed SNP chips, which test genetic variation at hundreds-of-thousands of specific locations across the genome. ....

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