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Cytotherapy
. 2023 Oct 28:S1465-3249(23)01056-3.
doi: 10.1016/j.jcyt.2023.10.002. Online ahead of print. Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210)
Cristina Ferreras 1 , Clara Hernández-Blanco 2 , Alejandro Martín-Quirós 3 , Karima Al-Akioui-Sanz 1 , Marta Mora-Rillo 4 , Fátima Ibáñez 5 , Mariana Díaz-Almirón 6 , Jordi Cano-Ochando 7 , Daniel Lozano-Ojalvo 8 , María Jiménez-González 9 , Rosa Goterris 10 , Elena Sánchez-Zapardiel 11 , Raquel de Paz 12 , Pilar Guerra-García 13 , Javier Queiruga-Parada 14 , Pablo Molina 14 , María Luisa Briones 15 , Beatriz Ruz-Caracuel 1 , Alberto M Borobia 16 , Antonio J Carcas 17 , Dolores Planelles 18 , José Luis Vicario 19 , Miguel Ángel Moreno 19 , Antonio Balas 19 , Marta Llano 20 , Andrea Llorente 20 , Álvaro Del Balzo 3 , Carlos Cañada 3 , Miguel Ángel García 3 , María Elena Calvin 3 , Isabel Arenas 3 , Rebeca Pérez de Diego 21 , Cristina Eguizábal 22 , Bernat Soria 23 , Carlos Solano 24 , Antonio Pérez-Martínez 25
Affiliations
Background aims: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment.
Methods: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population.
Results: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events.
Conclusions: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia.
Trial registration: NCT04578210.
Keywords: CD45RA(−) memory T cells; COVID-19; cell therapy; immune recovery; lymphopenia; viral diseases.
. 2023 Oct 28:S1465-3249(23)01056-3.
doi: 10.1016/j.jcyt.2023.10.002. Online ahead of print. Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210)
Cristina Ferreras 1 , Clara Hernández-Blanco 2 , Alejandro Martín-Quirós 3 , Karima Al-Akioui-Sanz 1 , Marta Mora-Rillo 4 , Fátima Ibáñez 5 , Mariana Díaz-Almirón 6 , Jordi Cano-Ochando 7 , Daniel Lozano-Ojalvo 8 , María Jiménez-González 9 , Rosa Goterris 10 , Elena Sánchez-Zapardiel 11 , Raquel de Paz 12 , Pilar Guerra-García 13 , Javier Queiruga-Parada 14 , Pablo Molina 14 , María Luisa Briones 15 , Beatriz Ruz-Caracuel 1 , Alberto M Borobia 16 , Antonio J Carcas 17 , Dolores Planelles 18 , José Luis Vicario 19 , Miguel Ángel Moreno 19 , Antonio Balas 19 , Marta Llano 20 , Andrea Llorente 20 , Álvaro Del Balzo 3 , Carlos Cañada 3 , Miguel Ángel García 3 , María Elena Calvin 3 , Isabel Arenas 3 , Rebeca Pérez de Diego 21 , Cristina Eguizábal 22 , Bernat Soria 23 , Carlos Solano 24 , Antonio Pérez-Martínez 25
Affiliations
- PMID: 37897472
- DOI: 10.1016/j.jcyt.2023.10.002
Background aims: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment.
Methods: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population.
Results: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events.
Conclusions: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia.
Trial registration: NCT04578210.
Keywords: CD45RA(−) memory T cells; COVID-19; cell therapy; immune recovery; lymphopenia; viral diseases.