Docta Complutense
Open Access Institutional Repository of the Complutense University of Madrid, that compiles scientific production to promote the visibility and impact of Complutense research.
With the collaboration of the Ministerio de Ciencia e Innovación and the Spanish Foundation for Science and Technology (FECYT).
Recent Submissions
GPA33-Targeted Trimeric Immunotoxin Exhibits Enhanced Antitumor Activity in Human Colorectal Cancer Xenografts
(International Journal of Molecular Sciences, 2026) Ruiz de la Herrán, Javier; Narbona Corral, Javier; García Gordo, Rubén; Sanz, Laura; Lacadena García-Gallo, Francisco Javier
Immunotoxins are chimeric molecules with high potential as therapeutic candidates that combine antibody specificity to recognize and bind tumor-associated antigens and the cytotoxic potency of the enzymatic activity of a toxin, leading to the selective death of target cells. The use of immunotoxins as therapeutic tools remains limited by various issues, such as selecting the appropriate tumor-associated antigen (TAA), penetration difficulties in solid tumors, low renal clearance, and low toxic payload. For this purpose, in this work we have designed a novel trimeric immunotoxin (IMTXTriA33αS) against colorectal cancer, combining the scFv against GPA33 as a targeting domain and the fungal ribotoxin α-sarcin (αS) as the toxic fragment, linked by a trimerization domain (TIEXVIII). Our results demonstrate that IMTXTriA33αS has greater avidity and toxic load, showing a very significant increase in its in vitro and in vivo antitumor efficacy, due to its trimeric structure.
The legacy of the paleotropical flora belt: extreme continental vicariance and island refugia in Woodwardioid ferns
(Molecular Phylogenetics and Evolution, 2026) Santos, Guillermo; Fernández Mazuecos Santa Teresa, Mario; Krause, Cornelia; Molino De Miguel, Sonia; Roth-Nebelsick, Anita; Thiv, Mike; Mairal Pisa, Mario José
The distribution of vegetation across the Northern Hemisphere has been profoundly shaped by the climatic and geological history of the Cenozoic. An ancient paleotropical vegetation belt, once spanning the Northern Hemisphere, is hypothesized to have facilitated biotic exchange across regions during the early Cenozoic, before its eventual fragmentation and near-complete disappearance. We investigate the evolutionary history of this pattern using the fern subfamily Woodwardioideae (Blechnaceae)—a striking example of disjunction across the Northern Hemisphere. By integrating phylogenetic relationships, divergence times and ancestral range dynamics based on plastid and genome-wide genotyping-by-sequencing markers, complemented by a review of the fossil record, ecological niche modelling and paleoclimate simulations, we reconstruct the spatio–temporal colonization history of this group. Our results suggest a vicariance-driven speciation process facilitated by climatic change. Notably, we identify intracontinental vicariance between the sister species Woodwardia radicans and W. unigemmata across Eurasia in the Pliocene, likely driven by the extinction of intermediate populations, which confined these species to opposite ends of Eurasia, corresponding to late-Cenozoic refugia of the paleotropical (lauroid) element. Extinction in the Western Palearctic appears to have been more severe than in the East, leading continental populations of W. radicans to retreat to the Macaronesian archipelagos, from which they back-colonized small continental and Mediterranean island enclaves in the Pleistocene. These findings underscore the role of islands as both crucial reservoirs for paleotropical-affinity relicts and sources of diversity for adjacent continental enclaves. They also emphasize both island and continental refugia as the last reservoirs of the evolutionary legacy of paleotropical-affinity lineages, and highlight their vulnerability to ongoing climate change.