Clinically compliant spatial and temporal imaging of chimeric antigen receptor T-cells.

The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19 B-cell malignancy has established a new therapeutic pillar of hematology-oncology. Nonetheless, formidable challenges remain for the attainment of comparable success in patients with solid tumors. To accelerate progress and rapidly characterize emerging toxicities, systems that permit the repeated and non-invasive assessment of CAR T-cell bio-distribution would be invaluable.

Dynamic imaging for CAR-T-cell therapy.

Chimaeric antigen receptor (CAR) therapy is entering the mainstream for the treatment of CD19(+)cancers. As is does we learn more about resistance to therapy and the role, risks and management of toxicity. In solid tumour CAR therapy research the route to the clinic is less smooth with a wealth of challenges facing translating this, potentially hugely valuable, therapeutic option for patients.

Resistance--the true face of biological defiance.

Biological therapeutics are widely used in chronic inflammatory and malignant disease. The underlying mechanisms of treatment failure for these drugs are poorly understood. Resistance to these biological agents and the further subdivision into intrinsic and acquired resistance are not clearly defined.

Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice.

The majority of human pancreatic cancers have activating mutations in the KRAS proto-oncogene. These mutations result in increased activity of the NF-κB pathway and the subsequent constitutive production of proinflammatory cytokines. Here, we show that inhibitor of κB kinase 2 (Ikk2), a component of the canonical NF-κB signaling pathway, synergizes with basal Notch signaling to upregulate transcription of primary Notch target genes, resulting in suppression of antiinflammatory protein expression and promotion of pancreatic carcinogenesis in mice.