Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study.

Background: Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.

Methods: This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma.

Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors.

Discovery of progenitor cell signatures by time-series synexpression analysis during Drosophila embryonic cell immortalization.

The use of time series profiling to identify groups of functionally related genes (synexpression groups) is a powerful approach for the discovery of gene function. Here we apply this strategy during Ras(V12) immortalization of Drosophila embryonic cells, a phenomenon not well characterized. Using high-resolution transcriptional time-series datasets, we generated a gene network based on temporal expression profile similarities.

Evolutionary plasticity of segmentation clock networks.

The vertebral column is a conserved anatomical structure that defines the vertebrate phylum. The periodic or segmental pattern of the vertebral column is established early in development when the vertebral precursors, the somites, are rhythmically produced from presomitic mesoderm (PSM). This rhythmic activity is controlled by a segmentation clock that is associated with the periodic transcription of cyclic genes in the PSM.

Comparison of pattern detection methods in microarray time series of the segmentation clock.

While genome-wide gene expression data are generated at an increasing rate, the repertoire of approaches for pattern discovery in these data is still limited. Identifying subtle patterns of interest in large amounts of data (tens of thousands of profiles) associated with a certain level of noise remains a challenge. A microarray time series was recently generated to study the transcriptional program of the mouse segmentation clock, a biological oscillator associated with the periodic formation of the segments of the body axis.

Segmental patterning of the vertebrate embryonic axis.

The body axis of vertebrates is composed of a serial repetition of similar anatomical modules that are called segments or metameres. This particular mode of organization is especially conspicuous at the level of the periodic arrangement of vertebrae in the spine. The segmental pattern is established during embryogenesis when the somites--the embryonic segments of vertebrates--are rhythmically produced from the paraxial mesoderm.

A complex oscillating network of signaling genes underlies the mouse segmentation clock.

The segmental pattern of the spine is established early in development, when the vertebral precursors, the somites, are rhythmically produced from the presomitic mesoderm. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the oscillator associated with this process, the segmentation clock, drives the periodic expression of a large network of cyclic genes involved in cell signaling. Mutually exclusive activation of the notch-fibroblast growth factor and Wnt pathways during each cycle suggests that coordinated regulation of these three pathways underlies the clock oscillator.

Synchronised cycling gene oscillations in presomitic mesoderm cells require cell-cell contact.

Segmentation of the vertebrate body axis is initiated early in development with the sequential formation of somites. Somitogenesis is temporally regulated by a molecular oscillator, the segmentation clock, which acts within presomitic mesoderm (PSM) cells to drive periodic expression of the cyclic genes. We have investigated the kinetics of the progression of cycling gene expression along the PSM.

Chicken genome: new tools and concepts.

Last spring, the Second International Chicken Genome Workshop was held at the Stowers Institute for Medical Research, less than 2 months after the first draft of the chicken genome was publicly released in March, 2004. This major event was highly anticipated by the chicken community, because of the invaluable resources that would be newly provided. In addition, from an evolutionary standpoint, birds are the species most closely related to mammals, whose genome has been sequenced.