Background CAR T cell therapy is a promising therapeutic modality for cancer treatment, but poor CAR T cell persistence limits efficacy in patients.1 CAR T cells with a memory-like phenotype are associated with durable persistence in patients and response to therapy,2 thereby implicating memory as an important therapeutic axis. Thus, strategies to stably promote CAR… Continue reading 247 FOXO1 is a master regulator of CAR T memory programming
Tag: Metabolic Pathways
258 Enhancing tumor infiltration of CAR T cells in solid tumors
AI SummaryCD8+ naive T cells undergo clonal expansion upon antigen encounter, giving rise to effector cells that eliminate infected and malignant cells. A subset of memory precursor effector cells survive contraction and become tissue-resident memory T (TRM) cells, providing long-term protection. This study aims to understand the molecular networks controlling TRM tissue infiltration and persistence… Continue reading 258 Enhancing tumor infiltration of CAR T cells in solid tumors
286 Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity
Background Chimeric antigen receptor (CAR) T-cell therapy in solid tumors has been largely disappointing. A key obstacle is the pre-existing antigenic heterogeneity, where not all tumor cells express the antigen targeted by the CAR. Antigen spreading (AS) is the induction and amplification of immune responses to secondary antigens distinct from the original therapeutic target. AS… Continue reading 286 Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity
280 Multiplex immunofluorescence imaging of armored CAR T cells in pancreatic ductal adenocarcinoma mouse xenografts confirms potent anti-tumor response
AI SummaryArmored CAR T cells were studied in a xenograft model of pancreatic ductal adenocarcinoma (PDAC). The study used imaging technology to understand the mechanism of action of armored CAR T cells and demonstrated their superior tumor penetration and killing abilities. This research provides insights into improving CAR T cell therapy for solid tumors.Background Chimeric… Continue reading 280 Multiplex immunofluorescence imaging of armored CAR T cells in pancreatic ductal adenocarcinoma mouse xenografts confirms potent anti-tumor response
275 Inosine endows CAR T cells with features of increased stemness and anti-tumor potency
AI SummaryExhausted CAR T cells produce adenosine, causing immune suppression. Overexpressing ADA-TM, which metabolizes adenosine, improves the function of exhausted CAR T cells. Inosine exposure enhances the metabolic and epigenetic state of CAR T cells. Inosine during cell manufacturing improves the efficacy of CAR T cell therapy.Background CAR T cells have been highly effective against… Continue reading 275 Inosine endows CAR T cells with features of increased stemness and anti-tumor potency
273 Hypermetabolic expansion conditions imprint lasting dysfunction on adoptive cell therapies
Background Adoptive cell therapies, like chimeric antigen receptor (CAR) T cell therapy act by redirecting and enhancing a patient’s immune response to tumor cells, with success in hematologic malignancies. However, many patients relapse due to failure of persistence of cells. Further, efficacy of cellular therapies is limited by barriers like poor tumor infiltration and an… Continue reading 273 Hypermetabolic expansion conditions imprint lasting dysfunction on adoptive cell therapies
246 Disruption of the cytokine signaling checkpoint CIS enhances serial-killing and anti-tumor activity of CAR-engineered {gamma}{delta} T cells
Background T cells have emerged as a promising allogeneic cell-based immunotherapy platform for the treatment of cancer. Armed with a unique combination of innate and adaptive immunity to target malignant cells, the infiltration and presence of T cells in various solid tumors is significantly correlated with survival benefit. Additional modifications to engineer T cells to… Continue reading 246 Disruption of the cytokine signaling checkpoint CIS enhances serial-killing and anti-tumor activity of CAR-engineered {gamma}{delta} T cells
234 Metabolic enhancement of alternately co-stimulated CART cells through AMPK creates functionally distinct phenotypes
AI SummaryChimeric antigen receptor (CAR) T cells can be improved by increasing their metabolic capacity through manipulation of cellular metabolism. Overexpression of AMPK2 increases the oxidative capacity of CART cells and enhances the inflammatory capacity of CD28-CARTs, while improving the in vitro expansion and central memory yield of 41BB-CARTs. These findings suggest that metabolic reprogramming… Continue reading 234 Metabolic enhancement of alternately co-stimulated CART cells through AMPK creates functionally distinct phenotypes
211 Spatial whole transcriptome profiling of human normal liver and HCC uncovers unique insights into metabolic zonation
Background Understanding the physiology and functions of the liver and cancer requires the knowledge of transcriptional patterns driving biological activities within the functional structures of the tissue, especially the zonated features of the liver metabolic networks. Methods Using the powerful and unique capabilities of GeoMx® Digital Spatial Profiler (DSP) with the Whole Transcriptome Atlas (WTA)… Continue reading 211 Spatial whole transcriptome profiling of human normal liver and HCC uncovers unique insights into metabolic zonation
171 Scalable liquid biopsy assay for treatment selection and MRD detection in lymphoma and its validation in novel live cell assays
AI SummaryResearchers developed protocols for enriching and preserving live B-cells and T-cells from blood to test in a live cell assay. They used the clinically validated OneRNA platform to identify new targets and biomarkers for response in lymphoma patients. The data correlated with treatment response, and the assay was able to identify additional treatment options.… Continue reading 171 Scalable liquid biopsy assay for treatment selection and MRD detection in lymphoma and its validation in novel live cell assays