Evaluation of the Safety and Efficacy of Autologous COVID-19 Antigen Specific T Cell in Prolonged SARS-CoV-2 Patients

Summary

The goal of this clinical study is to evaluate the safety and efficacy of autologous COVID-19 antigen specific T cell (LB-DTK-COV19) treatment in prolonged SARS-CoV-2 infected patients. The main questions it aims to answer are: * What adverse events occur after the infusion of LB-DTK-COV19? * Is there a clinically significant improvement in clinical symptoms within 4 weeks after the infusion? * Is there a clinically significant reduction in SARS-CoV-2 viral load within 4 weeks after the infusion? The patients will: * Receive a single infusion of LB-DTK-COV19 either intravenously or using central venous catheter during the baseline visit at a dose of 1x10\^7/m\^2. * Receive a second infusion of LB-DTK-COV19 either intravenously or using central venous catheter at the same dose 14 days after the first infusion. * Attend follow-up visits at the clinic for 6 months after the first infusion.

Timeline

Start

2023-06-08

Primary completion

2024-05-31

Completion

2025-01-22

Publications

• Background Kim N, Lee JM, Oh EJ, Jekarl DW, Lee DG, Im KI, Cho SG. Off-the-Shelf Partial HLA Matching SARS-CoV-2 Antigen Specific T Cell Therapy: A New Possibility for COVID-19 Treatment. Front Immunol. 2021 Dec 23;12:751869. doi: 10.3389/fimmu.2021.751869. eCollection 2021.
• Background Basar R, Uprety N, Ensley E, Daher M, Klein K, Martinez F, Aung F, Shanley M, Hu B, Gokdemir E, Nunez Cortes AK, Mendt M, Reyes Silva F, Acharya S, Laskowski T, Muniz-Feliciano L, Banerjee PP, Li Y, Li S, Melo Garcia L, Lin P, Shaim H, Yates SG, Marin D, Kaur I, Rao S, Mak D, Lin A, Miao Q, Dou J, Chen K, Champlin RE, Shpall EJ, Rezvani K. Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy. Cell Rep. 2021 Jul 20;36(3):109432. doi: 10.1016/j.celrep.2021.109432. Epub 2021 Jul 7.
• Background Keller MD, Harris KM, Jensen-Wachspress MA, Kankate VV, Lang H, Lazarski CA, Durkee-Shock J, Lee PH, Chaudhry K, Webber K, Datar A, Terpilowski M, Reynolds EK, Stevenson EM, Val S, Shancer Z, Zhang N, Ulrey R, Ekanem U, Stanojevic M, Geiger A, Liang H, Hoq F, Abraham AA, Hanley PJ, Cruz CR, Ferrer K, Dropulic L, Gangler K, Burbelo PD, Jones RB, Cohen JI, Bollard CM. SARS-CoV-2-specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein. Blood. 2020 Dec 17;136(25):2905-2917. doi: 10.1182/blood.2020008488.
• Background Cooper RS, Fraser AR, Smith L, Burgoyne P, Imlach SN, Jarvis LM, Turner DM, Zahra S, Turner ML, Campbell JDM. Rapid GMP-Compliant Expansion of SARS-CoV-2-Specific T Cells From Convalescent Donors for Use as an Allogeneic Cell Therapy for COVID-19. Front Immunol. 2021 Jan 8;11:598402. doi: 10.3389/fimmu.2020.598402. eCollection 2020.
• Background Ferreras C, Pascual-Miguel B, Mestre-Duran C, Navarro-Zapata A, Clares-Villa L, Martin-Cortazar C, De Paz R, Marcos A, Vicario JL, Balas A, Garcia-Sanchez F, Eguizabal C, Solano C, Mora-Rillo M, Soria B, Perez-Martinez A. SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy. Front Cell Dev Biol. 2021 Feb 25;9:620730. doi: 10.3389/fcell.2021.620730. eCollection 2021.
• Background Guerreiro M, Aguilar-Gallardo C, Montoro J, Frances-Gomez C, Latorre V, Luna I, Planelles D, Carrasco MP, Gomez MD, Gonzalez-Barbera EM, Aguado C, Sempere A, Solves P, Gomez-Segui I, Balaguer-Rosello A, Louro A, Perla A, Larrea L, Sanz J, Arbona C, de la Rubia J, Geller R, Sanz MA, Sanz G, Luis Pinana J. Adoptive transfer of ex vivo expanded SARS-CoV-2-specific cytotoxic lymphocytes: A viable strategy for COVID-19 immunosuppressed patients? Transpl Infect Dis. 2021 Aug;23(4):e13602. doi: 10.1111/tid.13602. Epub 2021 Mar 31.
• Background Papayanni PG, Chasiotis D, Koukoulias K, Georgakopoulou A, Iatrou A, Gavriilaki E, Giannaki C, Bitzani M, Geka E, Tasioudis P, Chloros D, Fylaktou A, Kioumis I, Triantafyllidou M, Dimou-Besikli S, Karavalakis G, Boutou AK, Siotou E, Anagnostopoulos A, Papadopoulou A, Yannaki E. Vaccinated and Convalescent Donor-Derived Severe Acute Respiratory Syndrome Coronavirus 2-Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients. Clin Infect Dis. 2021 Dec 6;73(11):2073-2082. doi: 10.1093/cid/ciab371.
• Background Perez-Martinez A, Mora-Rillo M, Ferreras C, Guerra-Garcia P, Pascual-Miguel B, Mestre-Duran C, Borobia AM, Carcas AJ, Queiruga-Parada J, Garcia I, Sanchez-Zapardiel E, Gasior M, De Paz R, Marcos A, Vicario JL, Balas A, Moreno MA, Eguizabal C, Solano C, Arribas JR, Buckley RM, Montejano R, Soria B. Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE). EClinicalMedicine. 2021 Sep;39:101086. doi: 10.1016/j.eclinm.2021.101086. Epub 2021 Aug 13.
• Background Martits-Chalangari K, Spak CW, Askar M, Killian A, Fisher TL, Atillasoy E, Marshall WL, McNeel D, Miller MD, Mathai SK, Gottlieb RL. ALVR109, an off-the-shelf partially HLA matched SARS-CoV-2-specific T cell therapy, to treat refractory severe COVID-19 pneumonia in a heart transplant patient: Case report. Am J Transplant. 2022 Apr;22(4):1261-1265. doi: 10.1111/ajt.16927. Epub 2021 Dec 27.
• Background Lee CY, Shah MK, Hoyos D, Solovyov A, Douglas M, Taur Y, Maslak P, Babady NE, Greenbaum B, Kamboj M, Vardhana SA. Prolonged SARS-CoV-2 Infection in Patients with Lymphoid Malignancies. Cancer Discov. 2022 Jan;12(1):62-73. doi: 10.1158/2159-8290.CD-21-1033. Epub 2021 Nov 9.
• Results Lee R, Kim N, Kim WB, Im KI, Nho D, Cho SY, Park C, Beck KS, Lee G, Lee I, Cho SG, Lee DG. Effectiveness and Safety of Autologous Virus-Specific T-Cell Therapy for Persistent COVID-19 in People With Immunocompromise: A Clinical Trial Study. Clin Infect Dis. 2026 Feb 4;81(6):e510-e514. doi: 10.1093/cid/ciaf302.

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Indications