GÉTICA 2021

50 VII FORO DE I nmunología Traslacional e INMUNOTERAPIA DEL CÁNCER inflammatory environment and immune modulation could be essential instead of their killing potency. To confirm it, in vivo ex- periments have to be considered. 2. Altogether, our findings will raise CIML-NK cells as a promising step forward in sarco- ma treatment. Conclusions: 1. Our results demonstrate that CIML-NK cells acquire potent anti-tumor capabilities against sarcoma cells, manifested by their enhanced IFN? production. Otherwise, re- sults obtained by long-term cytotoxicity ex- periments suggest that CIML-NK cell-derived CC-12. OVERCOMING CAR-MEDIATED CD19 DOWNMODULATION AND LEUKEMIA RELAPSE WITH T LYMPHOCYTES SECRETING ANTI-CD19 T CELL ENGAGERS Ramírez-Fernández, Ángel 1,2 ; Blanco, Belén 1,2 ; Bueno, Clara 3-5 ; Argemí-Muntadas, Lidia 6 ; Fuentes, Patricia 7 ; Aguilar-Sopeña, Óscar 8,9 ; Gutiérrez-Agüera, Francisco 3,4 ; Tapia-Galisteo, Antonio 10 ; Díez-Alonso, Laura 1,2 ; Segura-Tudela, Alejandro 1,2 ; Compte, Marta 10 ; Jiménez-Reinoso, Anaïs 1,2 ; Paz-Artal, Estela 1,8 ; Guedan, Sonia 11 ; Sanz, Laura 10 ; Toribio, María L. 7 ; Roda-Navarro, Pedro 8,9 ; Juan, Manel 12,13-15 ; Menéndez, Pablo 3-5,16,17 ; Álvarez-Vallina, Luis 1,2,6 1 Cancer Immunotherapy Unit (UNICA). Department of Immunology. Hospital Universitario 12 de Octubre. Madrid, Spain. 2 Immuno-Oncology and Immunotherapy Group. Instituto de Investigación Sanitaria 12 de Octubre (Imas12). Madrid, Spain. 3 Instituto de Ingestigación contra la Leucemia Josep Carreras. Barcelona, Spain. 4 RICORS-RETAV. Instituto de Salud Carlos III. Madrid, Spain. 5 Centro de Investigación Biomédica en Red-Oncología (CIBERONC). Instituto de Salud Carlos III. Madrid, Spain. 6 Immunotherapy and Cell Engineering Laboratory. Department of Engineering. Aarhus Universitet. Aarhus, Denmark. 7 Centro de BiologíaMolecular Severo Ochoa. CSIC-UAM. Madrid, Spain. 8 Department of Immunology, Ophthalmology and ENT. School of Medicine. Universidad Complutense. Madrid, Spain. 9 Lymphocyte Immunobiology Group. Instituto de Investigación Sanitaria 12 de Octubre (Imas12). Madrid, Spain. 10 Molecular Immunology Unit. Hospital Universitario Puerta de Hierro Majadahonda. Majadahonda. Madrid, Spain. 11 Department of Hematology and Oncology. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). Hospital Clinic. Barcelona, Spain. 12 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). Hospital Clínic. Barcelona, Spain. 13 Servei d’Immunologia. Hospital Clínic. Barcelona, Spain. 14 Plataforma Immunoteràpia. Hospital Sant Joan de Déu. Barcelona, Spain. 15 Universitat de Barcelona. Barcelona, Spain. 16 Department of Biomedicine. School of Medicine. Universitat de Barcelona. Barcelona, Spain. 17 Institució Catalana de Recerca i Estudis Avançats (ICREA). Barcelona, Spain neration (CD8TM‒4-1BB‒CD3 ζ ) anti-CD19 CAR and an anti-CD19/CD3 BiTE, both using the clinically-validated anti-CD19 A3B1 sin- gle-chain fragment variable (scFv), were ge- nerated. Anti-CD19 CAR (19-CAR) expression and anti-CD19/CD3 BiTE (19-BiTE) expres- sion and secretion were assessed by Wes- tern blot and/or flow cytometry in vitro and in vivo STAb-T19 and CAR-T19 activation (Fig. 1) Objectives: The aim of this project was to compare the efficacy of engineered T cells either expressing a second-generation an- ti-CD19 CAR (CAR-T19) or secreting an anti- CD19/CD3 bispecific T cell engager (BiTE) antibody (STAb-T19). Materials and methods: Vector genera- tion: lentiviral vectors encoding a second-ge-