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  1. Article: Isolation of Functional SARS-CoV-2 Antigen-Specific T-Cells with Specific Viral Cytotoxic Activity for Adoptive Therapy of COVID-19.

    García-Ríos, Estéfani / Leivas, Alejandra / Mancebo, Francisco J / Sánchez-Vega, Laura / Lanzarot, Diego / Aguado, José María / Martínez-López, Joaquín / Paciello, María Liz / Pérez-Romero, Pilar

    Biomedicines

    2022  Volume 10, Issue 3

    Abstract: In order to demonstrate the feasibility of preparing clinical-grade SARS-CoV-2-specific T-cells from convalescent donors and the ability of these cells to neutralize the virus in vitro, we used blood collected from two COVID-19 convalescent donors ( ... ...

    Abstract In order to demonstrate the feasibility of preparing clinical-grade SARS-CoV-2-specific T-cells from convalescent donors and the ability of these cells to neutralize the virus in vitro, we used blood collected from two COVID-19 convalescent donors (before and after vaccination) that was stimulated with specific SARS-CoV-2 peptides followed by automated T-cell isolation using the CliniMacs Prodigy medical device. To determine cytotoxic activity, HEK 293T cells were transfected to express the SARS-CoV-2 M protein, mimicking SARS-CoV-2 infection. We were able to quickly and efficiently isolate SARS-CoV-2-specific T lymphocytes from both donors before and after they received the Pfizer-BioNTech vaccine. Althoughbefore vaccination, the final product contained up to 7.42% and 30.19% of IFN-γ+ CD3+ T-cells from donor 1 and donor 2, respectively, we observed an enrichment of the IFN-γ+ CD3+ T-cells after vaccination, reaching 70.47% and 42.59%, respectively. At pre-vaccination, the isolated SARS-CoV-2-specific T-cells exhibited cytotoxic activity that was significantly higher than that of unstimulated controls (donor 2: 15.41%,
    Language English
    Publishing date 2022-03-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10030630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma.

    Leivas, Alejandra / Valeri, Antonio / Córdoba, Laura / García-Ortiz, Almudena / Ortiz, Alejandra / Sánchez-Vega, Laura / Graña-Castro, Osvaldo / Fernández, Lucía / Carreño-Tarragona, Gonzalo / Pérez, Manuel / Megías, Diego / Paciello, María Liz / Sánchez-Pina, Jose / Pérez-Martínez, Antonio / Lee, Dean A / Powell, Daniel J / Río, Paula / Martínez-López, Joaquín

    Blood cancer journal

    2021  Volume 11, Issue 8, Page(s) 146

    Abstract: CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be designed through the use of receptors, such as NKG2D, ... ...

    Abstract CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be designed through the use of receptors, such as NKG2D, which recognizes a wide range of ligands to provide broad target specificity. Here, we test this approach by analyzing the antitumor activity of activated and expanded NK cells (NKAE) and CD45RA
    MeSH term(s) Animals ; Cell Line, Tumor ; Humans ; Immunotherapy, Adoptive/methods ; Killer Cells, Natural/transplantation ; Male ; Mice, Inbred NOD ; Multiple Myeloma/therapy ; NK Cell Lectin-Like Receptor Subfamily K/therapeutic use ; Mice
    Chemical Substances KLRK1 protein, human ; NK Cell Lectin-Like Receptor Subfamily K
    Language English
    Publishing date 2021-08-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2600560-8
    ISSN 2044-5385 ; 2044-5385
    ISSN (online) 2044-5385
    ISSN 2044-5385
    DOI 10.1038/s41408-021-00537-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Real-world effectiveness of caplacizumab vs standard of care in immune thrombotic thrombocytopenic purpura.

    Pascual Izquierdo, Maria Cristina / Mingot-Castellano, Maria Eva / Kerguelen Fuentes, Ana Esther / García-Arroba Peinado, José / Cid, Joan / Jiménez, Moraima / Valcarcel, David / Gomez-Segui, Ines / de la Rubia, Javier / Martin, Paz / Goterris, Rosa / Hernández-Mateo, Luis M / Tallón Ruiz, Inmaculada / Varea, Sara / Fernández-Docampp, Marta / García-Muñoz, Nadia / Vara, Míriam / Fernández Zarzoso, Miguel / García-Candel, Faustino /
    Paciello, María Liz / García-García, Irene / Zalba, Saioa / Campuzano Saavedra, Verónica / Garcia-Gala, José Mª M / Vidan, Julia / Moreno, Gemma / Lopez Lorenzo, Jose Luis / González Arias, Elena / Freiría, Carmen / Solé, María / Ávila Idrovo, Laura Francisca / Hernández Castellet, José Carlos / Cruz, Naylen / Lavilla, Esperanza / Pérez-Montaña, Albert / Atucha, Jon Ander / Moreno Beltrán, María Esperanza / Romero Macías, Juan-Ramón / Salinas Argente, Ramon / Del Rio-Garma, Julio

    Blood advances

    2022  

    Abstract: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with PEX and immunosuppression. The objective of this ... ...

    Abstract Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with PEX and immunosuppression. The objective of this study is to analyze and compare the safety and efficacy of caplacizumab versus the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 iTTP patients (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5% p<0.05) and less refractoriness (4.5% vs 14.1% p<0.05) than those that were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after plasma exchange (PEX) was associated with a lower number of PEX (OR 7.5, CI 2.3-12.7; p<0.05) and days of hospitalization (OR 11.2, CI 5.6-16.9; p<0.001) compared to standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared to the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared to standard of care regimens. When administered within the first 3 days after PEX it also provided a faster clinical response, reducing hospitalization time and the need for PEX.
    Language English
    Publishing date 2022-08-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2022008028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

    Avendano-Sola, Cristina / Ramos-Martinez, Antonio / Munez-Rubio, Elena / Ruiz-Antoran, Belen / Malo de Molina, Rosa / Torres, Ferran / Fernandez-Cruz, Ana / Callejas-Diaz, Alejandro / Calderon, Jorge / Payares-Herrera, Concepcion / Salcedo, Isabel / Romera, Irene / Lora-Tamayo, Jaime / Mancheno-Losa, Mikel / Paciello, Maria Liz / Villegas, Carolina / Estrada, Vicente / Saez-Serrano, Isabel / Porras-Leal, Maria Lourdes /
    Jarilla-Fernandez, Maria del Castillo / Pano-Pardo, Jose Ramon / Moreno-Chulilla, Jose Antonio / Arrieta-Aldea, Itziar / Bosch, Alba / Belhassen-Garcia, Moncef / Lopez-Villar, Olga / Ramos-Garrido, Ascension / Blanco, Lydia / Madrigal, Maria Elena / Contreras, Enric / Muniz-Diaz, Eduard / Domingo-Morera, Jose Maria / Casas-Flecha, Inmaculada / Perez-Olmeda, Mayte / Garcia-Perez, Javier / Alcami, Jose / Bueno, Jose Luis / Duarte, Rafael F

    medRxiv

    Abstract: Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized ... ...

    Abstract Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).
    Keywords covid19
    Language English
    Publishing date 2020-09-01
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.08.26.20182444
    Database COVID19

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