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Mutant Gene-Targeted Immunotherapy Approach Developed

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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, [email protected], or Valerie Mehl, 410-614-2916, [email protected]. Brookhaven Lab media contacts: Cara Laasch, 631-344-8458, [email protected] or Peter Genzer, 631-344-3174, [email protected]. ....

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Cancer immunotherapy approach targets common genetic alteration

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IMAGE: Novel cancer immunotherapy approach inverts a missing gene copy into an immune cell-activating signal.
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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. ....

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Targeting a neoantigen derived from a common TP53 mutation

Targeting a neoantigen derived from a common TP53 mutation
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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 ....

United States , Michaelb Murphy , Shibin Zhou , Emily Han , Nickolas Papadopoulos , Michael Hwang , Evangeline Watson , Katharine Wright , Astra Zeneca Medimmune Amplimmune , Katharinem Wright , Yana Li , Patricka Brown , Gabriel Ghiaur , Bristol Myers Squibb , Bert Vogelstein , Kenneth Kinzler , Suman Paul , P Aitana Azurmendi , Sandra Gabelli , Chetan Bettegowda , Chung Hsiue , Michelles Miller , Andrew Skora , Sarahr Dinapoli , Andrewd Skora , Alexanderh Pearlman ,