ICOS costimulation at the tumor site in combination with CTLA-4 blockade therapy elicits strong tumor immunity

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) blockade therapy is able to induce long-lasting antitumor responses in a fraction of cancer patients. Nonetheless, there is still room for improvement in the quest for new therapeutic combinations. ICOS costimulation has been underscored as a possible target to include with CTLA-4 blocking treatment. Herein, we describe an ICOS agonistic aptamer that potentiates T cell activation and induces stronger antitumor responses when locally injected at the tumor site in combination with anti-CTLA-4 antibody in different tumor models. Furthermore, ICOS agonistic aptamer was engineered as a bi-specific tumor-targeting aptamer to reach any disseminated tumor lesions after systemic injection. Treatment with the bi-specific aptamer in combination with CTLA-4 blockade showed strong antitumor immunity, even in a melanoma tumor model where CTLA-4 treatment alone did not display any significant therapeutic benefit. Thus, this work provides strong support for the development of combinatorial therapies involving anti-CTLA-4 blockade and ICOS agonist tumor-targeting agents

ICOS costimulation at the tumor site in combination with CTLA-4 blockade therapy elicits strong tumor immunity

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) blockade therapy is able to induce long-lasting antitumor responses in a fraction of cancer patients. Nonetheless, there is still room for improvement in the quest for new therapeutic combinations. ICOS costimulation has been underscored as a possible target to include with CTLA-4 blocking treatment. Herein, we describe an ICOS agonistic aptamer that potentiates T cell activation and induces stronger antitumor responses when locally injected at the tumor site in combination with anti-CTLA-4 antibody in different tumor models. Furthermore, ICOS agonistic aptamer was engineered as a bi-specific tumor-targeting aptamer to reach any disseminated tumor lesions after systemic injection. Treatment with the bi-specific aptamer in combination with CTLA-4 blockade showed strong antitumor immunity, even in a melanoma tumor model where CTLA-4 treatment alone did not display any significant therapeutic benefit. Thus, this work provides strong support for the development of combinatorial therapies involving anti-CTLA-4 blockade and ICOS agonist tumor-targeting agents

The structure of the pelagic ecosystem related to oceanographic and topographic features in the Gulf of Cadiz, Straits of Gibraltar and Alborán Sea during July 1995

Se analizan los resultados obtenidos en 59 estaciones muestreadas en el golfo de Cádiz, el estrecho de Gibraltar y el sector noroeste del mar de Alborán, en julio de 1995. Se presentan las principales características hidrológicas registradas durante la prospección y su posible relación con las composiciones y distribuciones planctónicas. En el golfo de Cádiz, con aguas más someras, cálidas y de menor salinidad, predominan los huevos y lavas de boquerón Engraulis encrasicolus (L., 1758) y de alacha Sardinella aurita Valenciennes, 1847 (tipicamente costeros), mientras que en mar de Alborán, con plataforma estrecha y un afloramiento activo, el ictioplancton oceánico de Maurolicus muelleri (Gmelin, 1788) es el mayoritario. Las diferentes características topográficas y oceanográficas de ambas zonas también se han reflejado en los análisis complementarios realizados. Así, las aguas atlánticas se caracterizan por presentar valores inferiores en concentraciones (actividad nitrato reductasa, material particulado, clorofila a y feopigmentos), mayores concentraciones de fosfatos y mayor abundancia de grupos planctónicos de pequeño tamaño (bacterioplacton, picoplancton autótrofo, flagelados, ciliados, cladóceros y copépodos).The results obtained from 59 stations sampled in the Gulf of Cadiz, Straits of Gibraltar and Alborán Sea (northwest sector) during July 1995 are analysed in this paper. The main hydrological characteristics recorded during the survey and their possible relationship with planktonic distribution and composition are presented. The eggs and larvae of anchovy Engraulis encrasicolus (L., 1758) and gilt sardine Sardinella aurita Valenciennes, 1847 (typically coastal) were the most abundant in the Gulf of Cadiz, where warmer, fresher and shallower waters are dominant. However, the Maurolicus muelleri (Gmelin, 1788) plankton components (oceanic) predominated in the Alborán Sea, characterised by a narrow continental shelf and active upwelling. The different topographic and hydrographic features of these geographic zones were also apparent in the complementary analyses that were carried out: Atlantic waters were characterised by lower concentration values of nitrate reductase activity, particulate matter, chlorophyll-a and phaeopigments, and higher values of phosphate concentrations and small planktonic organisms (bacterioplankton, autotrophic picoplankton, flagellates, ciliates, cladocerans and copepods).Postprint

An RNA toolbox for cancer immunotherapy

Cancer immunotherapy has revolutionized oncology practice. However, current protein and cell therapy tools used in cancer immunotherapy are far from perfect, and there is room for improvement regarding their efficacy and safety. RNA-based structures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects and the ability to specifically bind different molecules. These functions make them versatile tools that may advance cancer vaccines and immunomodulation, surpassing existing approaches. These technologies should not be considered as competitors of current immunotherapies but as partners in synergistic combinations and as a clear opportunity to reach more efficient and personalized results. RNA and RNA derivatives can be exploited therapeutically as a platform to encode protein sequences, provide innate pro-inflammatory signals to the immune system (such as those denoting viral infection), control the expression of other RNAs (including key immunosuppressive factors) post-transcriptionally and conform structural scaffoldings binding proteins that control immune cells by modifying their function. Nascent RNA immunotherapeutics include RNA vaccines encoding cancer neoantigens, mRNAs encoding immunomodulatory factors, viral RNA analogues, interference RNAs and protein-binding RNA aptamers. These approaches are already in early clinical development with promising safety and efficacy results

100 años investigando el mar. El IEO en su centenario (1914-2014).

Se trata de un libro que pretende divulgar a la sociedad las principales investigaciones multidisciplinares llevadas a cabo por el Instituto Español de Oceanografía durante su primer siglo de vida, y dar a conocer la historia del organismo, de su Sede Central y de los nueve centros oceanográficos repartidos por los litorales mediterráneo y atlántico, en la península y archipiélagos.Kongsberg 200Postprin