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W155 - Cart-cell Therapy Directed Towards Novel CD84 Antigen for the Treatment of Acute Myeloid Leukemia

Wednesday, June 21, 2023
7:30 AM – 7:30 PM  
Lorena Pérez Amill – Fundació de Recerca Clínic Barcelona- IDIBAPS / Gyala Therapeutics / Hospital Clínic de Barcelona, Spain; Mercedes Armand Ugon – Fundació de Recerca Clínic Barcelona- IDIBAPS / Gyala Therapeutics / Hospital Clínic de Barcelona, Spain; Sergio Peña Pérez – Fundació de Recerca Clínic Barcelona- IDIBAPS / Gyala Therapeutics / Hospital Clínic de Barcelona, Spain; Maria Val Casals – Fundació de Recerca Clínic Barcelona- IDIBAPS / Gyala Therapeutics / Hospital Clínic de Barcelona, Spain; Claudio Santos – Gyala Therapeutics, Spain; Gerard Frigola – Hospital Clínic de Barcelona, Spain; Francesca Guijarro – Hospital Clínic de Barcelona, Spain; Alfredo Minguela – Clinic University Hospital Virgen de la Arrixaca & Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), Murcia, Spain; Àlex Bataller – Hospital Clínic de Barcelona, Spain; Berta Casanovas Albertí – Fundació de Recerca Clínic Barcelona- IDIBAPS / Hospital Clínic de Barcelona, Spain; Mireia Uribe Herranz – Fundació de Recerca Clínic Barcelona- IDIBAPS / Hospital Clínic de Barcelona, Spain; José Ramón Álamo – Hospital Clínic de Barcelona, Spain; Daniel Benítez Ribas – Hospital Clínic de Barcelona, Spain; Europa Azucena González Navarro – Hospital Clínic de Barcelona, Spain; Diego Sánchez Martínez – Josep Carreras Leukemia Research Institute, School of Medicine, University of Barcelona, Barcelona, Spain; talía Velasco Hernández – Josep Carreras Leukemia Research Institute, School of Medicine, University of Barcelona, Barcelona, Spain; Néstor Tirado – Josep Carreras Leukemia Research Institute, School of Medicine, University of Barcelona, Barcelona, Spain; Paola Alejandra Romecín – Josep Carreras Leukemia Research Institute, School of Medicine, University of Barcelona, Barcelona, Spain; Pablo Menéndez – Josep Carreras Leukemia Research Institute, School of Medicine, University of Barcelona, Barcelona, Spain; Antonio Martínez – Hospital Clínic de Barcelona, Spain; Montserrat Rovira – Hospital Clínic de Barcelona, Spain; Jordi Esteve – Fundació de Recerca Clínic Barcelona- IDIBAPS / Hospital Clínic de Barcelona, Spain; Álvaro Urbano Ispizua – Fundació de Recerca Clínic Barcelona- IDIBAPS / Hospital Clínic de Barcelona, Spain; Julio Delgado – Fundació de Recerca Clínic Barcelona- IDIBAPS/ Hospital Clínic de Barcelona/ University of Barcelona, Spain; Nela Klein González – Fundació de Recerca Clínic Barcelona- IDIBAPS / Hospital Clínic de Barcelona, Spain
Abstract Text: Acute myeloid leukemia (AML) is an heterogeneous malignancy with scarce treatment options in the relapsed or refractory (R/R) setting. CART cells have revolutionized the treatment of R/R multiple myeloma and B-cell malignancies; however, none has yet been approved for AML. CD84 (SLAMF5) is a member of the SLAM family of cell-surface immunoreceptors. Here, we validate the CD84 antigen as a novel target for AML and present a first-in-class CD84-directed CART cell (CART84) for AML.
Patient primary AML blasts were analyzed by flow cytometry: while CD84 was overexpressed on their surface in the majority of AML cases, both de novo and at relapse, its expression was very low in CD34+ healthy hematopoietic stem/progenitor cells (HSPC). Moreover, healthy human tissues were analyzed by immunohistochemistry and CD84 expression was not found in the lung, liver, kidney, myocardium, skin, or brain, except in tissue monocytes/macrophages. We engineered second-generation CART cells with murine or fully human single chain variable fragments (scFv) and 4-1BB as a co-stimulatory domain (anti-CD84scFv-CD8αTM-4-1BB-CD3). CART84 exerted high cytotoxicity in vitro towards AML cells even at low effector:target ratios. In terms of safety, CART84 displayed a very low cytotoxic effect towards CD34+ HSPC, suggesting that CART84 may be less myelotoxic than other CART cells in AML. CART84 eliminated AML cells in vivo in a NSG mouse model using both AML cell lines and a patient-derived-xenograft (PDX). In summary, these results validate CD84 as a potential target for AML CART-cell therapy and support the therapeutic use of CART84 for R/R AML patients.