268 Development of FT825/ONO-8250: an off-the-shelf CAR-T cell with preferential HER2 targeting and engineered to enable multi-antigen targeting, improve trafficking, and overcome immunosuppression

AI SummaryFT825/ONO-8250 is an engineered CAR-T cell therapy designed to address barriers in treating solid tumors. It targets HER2 and demonstrates potent and specific targeting of tumor cells. It resists tumor suppression and enhances migration to solid tumors. The therapy is scheduled for IND submission in 2023.Background Although effective in multiple liquid tumor indications, chimeric… Continue reading 268 Development of FT825/ONO-8250: an off-the-shelf CAR-T cell with preferential HER2 targeting and engineered to enable multi-antigen targeting, improve trafficking, and overcome immunosuppression

236 In vivo-generated TagCAR T cells inhibit solid tumor growth following treatment with bispecific small molecule TumorTags

AI SummaryUmoja has developed an off-the-shelf CAR T cell therapy called UB-VV200, which is generated in vivo using lentiviral vectors. They have also developed TumorTags, which are tumor antigen ligands conjugated to fluorescein. In vitro and in vivo experiments showed that UB-VV200 together with TumorTags have the potential to be a more accessible and affordable… Continue reading 236 In vivo-generated TagCAR T cells inhibit solid tumor growth following treatment with bispecific small molecule TumorTags

191 Expediting MxIF panel development in FFPE for the PhenoCycler platform: the ‘Joker panel development kit

Background Highly multiplexed cyclic immunofluorescence (MxIF) platforms, such as the PhenoCycler system (formerly CODEX) by Akoya Biosciences allow users to stain and visualize up to 100 markers on a single formalin-fixed paraffin-embedded (FFPE) tissue section. The Phenocycler accomplishes this feat by staining the tissue with antibodies that have been conjugated to a unique single-stranded oligonucleotide… Continue reading 191 Expediting MxIF panel development in FFPE for the PhenoCycler platform: the ‘Joker panel development kit

205 AI driven interrogation of spatial proteomic and transcriptomics atlases in the tumor microenvironment of triple negative breast cancer

AI SummaryResearchers have developed an automated AI-driven workflow that uses deep-learning algorithms to identify and select tumor regions for spatial-omic analysis in triple negative breast cancer (TNBC). This allows for the characterization of the tumor microenvironment and identification of potential biomarkers and drug targets.Background The limited efficacy of approved therapies for patients with triple negative… Continue reading 205 AI driven interrogation of spatial proteomic and transcriptomics atlases in the tumor microenvironment of triple negative breast cancer

204 Unveiling differential gene expression profiling and potential biomarker in breast cancer with the NanoString GeoMx digital spatial profiler

AI SummaryA study investigated the tumor microenvironment of breast cancer using spatial biology technology. The high expression levels of the ERBB2 gene in epithelial segments suggest its potential as a biomarker for breast cancer treatment. This study opens up possibilities for using spatial biology techniques to improve diagnostics and personalized treatment in breast cancer research.Background… Continue reading 204 Unveiling differential gene expression profiling and potential biomarker in breast cancer with the NanoString GeoMx digital spatial profiler

195 Overcoming the dose-response prediction limitation from bench to clinic for T-cell engagers: using quantitative systems pharmacology (QSP) modelling in the development of CDR404 for solid tumors

AI SummaryA quantitative systems pharmacology (QSP) model was developed to support the first-in-human trial design for a T-cell engager called CDR404. The model described the drug’s pharmacokinetics and dynamics of binding to tumor cells and T-cells. By fitting the parameters, the model was able to predict cytotoxicity and IFN release in vitro. The model was… Continue reading 195 Overcoming the dose-response prediction limitation from bench to clinic for T-cell engagers: using quantitative systems pharmacology (QSP) modelling in the development of CDR404 for solid tumors

110 Deep learning models identify key tumor microenvironment features associated with genetic signatures of UV mutagenesis and alkylating agent treatment in melanoma

AI SummaryMelanoma, a type of skin cancer, exhibits therapeutic resistance. This study used machine learning to analyze the tumor microenvironment in melanoma and found associations between TME features and genetic mutations caused by UV exposure and alkylating agent treatment. Tumor-infiltrating lymphocytes were associated with UV exposure, while neutrophils were associated with alkylating agents. The study… Continue reading 110 Deep learning models identify key tumor microenvironment features associated with genetic signatures of UV mutagenesis and alkylating agent treatment in melanoma

144 Novel public and tumor-wide neoantigens arising from clonal aberrant splicing events drive tumor-specific T-cell responses across diverse cancer types

Background Immunotherapy in gliomas is limited by tumor heterogeneity and low mutational burden. We developed a novel comprehensive in silico pipeline for detecting tumor-specific splicing events (neojunctions) across multiple cancer types, and in gliomas, we successfully identified tumor-wide, public, alternatively spliced neoantigens (ASNs) that elicit CD8+ T-cell-mediated immune responses. Methods Our pipeline identified recurring public… Continue reading 144 Novel public and tumor-wide neoantigens arising from clonal aberrant splicing events drive tumor-specific T-cell responses across diverse cancer types

147 Targeting a novel chimeric RNA, A-B, as a non-traditional therapeutic in colorectal cancer

Background Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide, affecting over 100,000 men and women in the United States every year. There is an urgent and unmet need for early biomarker discovery and the identification of novel therapeutic targets in CRC. Chimeric RNAs and their protein products, including BCR-ABL in chronic myelogenous… Continue reading 147 Targeting a novel chimeric RNA, A-B, as a non-traditional therapeutic in colorectal cancer

104 A spatial pharmacology approach to decipher drug-target-microenvironment interactions in situ

AI SummaryA new single-cell spatial pharmacology approach has been developed to analyze the interaction between therapeutic drugs and the tumor microenvironment at a cellular level. This technique allows for the identification of specific cell types targeted by therapeutic antibodies, as well as measuring antibody penetration into tumors. The method has the potential to uncover drug… Continue reading 104 A spatial pharmacology approach to decipher drug-target-microenvironment interactions in situ