Background Immune effector T-cells are a promising therapy due to their innate cytotoxicity. In particular, CAR T-cell therapy uses genetically engineered T-cells that express a chimeric antigen receptor that binds to a specific antigen on tumor cells. A key factor influencing CAR-T cell efficacy is the density of target antigens on cancer cells, which dictates… Continue reading 303 Exploring CAR-T cell killing dynamics through live-cell fluorescence microscopy
Tag: Enzyme Kinetics and Mechanisms
268 Next generation binding: measuring cell avidity to fully characterize cell-cell interactions and understand mechanism of action for cellular therapies
Background While conventional assays such as affinity, cytokine secretion, and cytotoxicity provide valuable data at a molecular level, this information is insufficient to fully characterize and select the best cellular therapies. There is still a lack of understanding about cell-cell interactions that drive functional processes. Methods Cell avidity, the collective strength of interactions between an… Continue reading 268 Next generation binding: measuring cell avidity to fully characterize cell-cell interactions and understand mechanism of action for cellular therapies
265 Manipulation of T cell signaling cascades for improved immunotherapy
Background CAR-T cells use TCR signaling cassettes coupled to the recognition elements of antibodies. While CAR-T technology has achieved significant success in treatment of certain liquid cancers, many challenges hinder the development of this therapy. CAR-T cells must be produced from the patient’s own T cells, which are often of poor quality and in short… Continue reading 265 Manipulation of T cell signaling cascades for improved immunotherapy
241 TIMING™-based functional single cell analysis reveals enhanced function of CAR T cells engineered using microfluidic vortex shedding
Background Cellular immunotherapy using chimeric antigen receptor T cell (CAR T) therapy has revolutionized treatment of patients with hematologic malignancy. Despite success, as many as half of leukemia patients experience disease progression. CAR T infusion product potency is often compromised by the poor health of T cells recovered from leukemia patients and intrinsic cellular mechanisms,… Continue reading 241 TIMING™-based functional single cell analysis reveals enhanced function of CAR T cells engineered using microfluidic vortex shedding
121 Exploring therapeutic potential: insights from drug penetration and targeting using Nilogens ex-vivo 3D-EXpress tumoroid platform
Background The effectiveness of therapeutics relies on their ability to penetrate and target solid tumors, often hindered by complex tumor-stroma architecture. Labeling therapeutics with fluorochromes aids in visualizing infiltration, binding, and internalization kinetics, enhancing our understanding of mechanisms of action for a given drug. Nilogen’s ex-vivo 3D-EXpress tumoroid platform retains the tumor microenvironment found in… Continue reading 121 Exploring therapeutic potential: insights from drug penetration and targeting using Nilogens ex-vivo 3D-EXpress tumoroid platform
147 A novel single-cell method using optical barcodes and machine learning to identify correlative biomarkers predictive of T cell function
Background Cell therapy has been successful for treating some hematological malignancies, largely through autologous chimeric antigen receptor (CAR) T-cell therapies. However, the complexity of CAR T-cell therapies makes them costly and time-consuming to develop. One of the major challenges is heterogeneity in CAR-T products due to underlying variability across the entire development process and the… Continue reading 147 A novel single-cell method using optical barcodes and machine learning to identify correlative biomarkers predictive of T cell function
196 Utilizing pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers to support recommended phase 2 dose (RP2D) selection for phase 1 study of SAR444245 (SAR245) in patients with advanced solid tumors
Background SAR’245 is a clinical-stage site-specific PEGylated human interleukin-2 (IL-2) that selectively engages IL-2 alpha receptor binding but retains near-native-binding affinity for beta/gamma complex. This results in a unique ‘T-cell remodeling’ mechanism of action (MoA) characterized by robust increase in CD8+ T cells coupled with potent natural killer (NK) cell activation/expansion without inducing regulatory T-cell… Continue reading 196 Utilizing pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers to support recommended phase 2 dose (RP2D) selection for phase 1 study of SAR444245 (SAR245) in patients with advanced solid tumors
38 SMART: a decentralized protocol for enhancing diverse patient representation in genomic research through remote monitoring and serial liquid biopsies
Background In research hospitals or academic centers, patients are actively engaged to participate in research. However, 80% of cancer patients are not treated in these institutions. This ‘invisible’ majority is under-represented in genomic research,1 leading to bias in the therapeutic pipeline since such research genomic data are the foundation informing drug target selection. This lack… Continue reading 38 SMART: a decentralized protocol for enhancing diverse patient representation in genomic research through remote monitoring and serial liquid biopsies
16 Engineering a chemokine/cytokine-releasing biopolymer scaffold to induce tertiary lymphoid-like structures
Background The presence of tumor-localized tertiary lymphoid structures (TLSs) has been increasingly shown to correlate with improved survival in certain solid tumor types.1-3 There is an unmet need to generate TLSs in tumors of patients where their absence is noted, with the intent to potentially improve outcomes. To address this, we employed murine models and… Continue reading 16 Engineering a chemokine/cytokine-releasing biopolymer scaffold to induce tertiary lymphoid-like structures
12 Comparative multi-omic analysis of antigen epitopes in gliomas
Background Gliomas are the most common primary central nervous system tumors in adults and have shown little response to most immunotherapies. Deciphering the antigen repertoire in gliomas and the contribution of different antigen types is crucial to better understanding anti-tumor immunity and for the development of multi-antigen targeted immunotherapies. While neoantigens and developmental tumor-associated antigens… Continue reading 12 Comparative multi-omic analysis of antigen epitopes in gliomas