Spanish National Cancer Research Centre

Design and Structure of Protein Cages Based on Helical Fusion and Machine Learning

ABSTRACT Self-assembling protein cages are versatile nanoscale architectures with broad applications in drug delivery, vaccine development, and structural biology. Historically, two main strategies have been used to construct such cages: genetic fusion of oligomeric domains conne...

Structural and single-molecule insights into the core human mitochondrial DNA replisome.

Replication of human mitochondrial DNA (mtDNA) is essential for the maintenance of oxidative phosphorylation and cellular energy homeostasis. Impairment of this process leads to mtDNA deletions, depletion, and point mutations that underlie a broad spectrum of mitochondrial diseas...

Functional assessment of inherited myeloid neoplasm‐associated SAMD9L germline variants via Monoallelic CRISPR modelling

Summary While the majority of myeloid neoplasms are sporadic, the increasing application of germline genetic testing has led the World Health Organization to designate ‘ Myeloid malignancies with germline predisposition’ as a distinct clinical entity, carrying major implications...

Tisa-cel and axi-cel CAR structure influences the development of resistance to CD19-CAR-T therapy

CD19-CAR-T cells are a major therapy for relapsed/refractory B-cell malignancies, yet ~50% of patients relapse after infusion. Clinical data suggest that tisa-cel treatment is associated with higher rates of CD19 mutation than axi-cel, though direct comparisons have been lacking....

DNA end-resection is stimulated by an interaction between BRCA1 exon 11 and TOPBP1

Abstract Approximately 60% of the tumour suppressor protein BRCA1 is encoded by a single exon. Many tumours carry mutations in this exon, often resulting in exon skipping and thus a protein of a severely reduced size. Although none of the well-described protein domains of BRCA1 a...

A Drug‐Gated, Modular STAb‐T Immunotherapy With External Control

ABSTRACT Living cell therapies lack robust, reversible mechanisms for externally controlling therapeutic activity after administration, limiting their safety and clinical adaptability. Here we engineer a drug‐gated cellular immunotherapy platform in which T cells function as prog...

Tumor Necrosis is Associated with an Increased Metastatic and Cardiovascular Risk in Paragangliomas: A Single-Center Series and Meta-Analysis Comparing Necrosis and Cystic Degeneration in Paragangliomas

Abstract Paragangliomas (PGLs) are rare neural crest–derived tumors with highly variable morphology and clinical behavior. These tumors can present with cystic and necrotic alterations that may influence the clinical presentation of affected patients. However, prevalence and clin...