A novel chimeric antigen receptor T-cell therapy targeting CD84 for the treatment of acute myeloid and T-cell lymphoblastic leukemias

Autores de IIS La Fe

• Alfredo Minguela Puras

  Autor

• Irene Navarro Vicente

  Autor

• Manuel Nuno Direito De Morais Guerreiro

  Autor

• Pau Montesinos Fernández

  Autor

Participantes ajenos a IIS La Fe

• Perez-Amill, Lorena
• Armand-Ugon, Mercedes
• Val-Casals, Maria
• Martin-Herreros, Beatriz
• Alamo, Jose R.
• Pena, Sergio
• Frigola, Gerard
• Altuna, Ane
• Santos, Claudio
• Guijarro, Francesca
• Bataller, Alex
• Casanovas-Alberti, Berta
• Uribe-Herranz, Mireia
• Sanchez-Martinez, Diego
• Tirado, Nestor
• Velasco-Hernandez, Talia
• Menendez, Pablo
• Martinez, Antonio
• Rovira, Montse
• Colomer, Dolors
• Gonzalez-Navarro, E. Azucena
• Esteve, Jordi
• Urbano-Ispizua, Alvaro
• Delgado, Julio
• Juan, Manel
• Klein-Gonzalez, Nela

Grupos

• Hematología y Hemoterapia

Abstract

Despite the remarkable clinical successes of chimeric antigen receptor (CAR) T-cell therapies in treating B-cell malignancies and multiple myeloma, similar outcomes have not been achieved in other indications. For patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or T-cell acute lymphoblastic leukemia (T-ALL), treatment options are limited, yet CART-cell therapies offer significant potential to address this unmet need. Here, we introduce a first-in-class CART-cell therapy targeting CD84, a novel antigen, for the treatment of R/R AML and T-ALL. CD84 is highly expressed on leukemic blasts, with limited expression on hematopoietic stem progenitor cells (HSPC), and is largely absent in healthy human tissues. Our second-generation CARTs targeting CD84 (CART84) demonstrate potent cytotoxicity against AML and T-ALL cells both in vitro and in vivo in patient-derived xenograft (PDX) models. Furthermore, CART84 eliminated primary leukemic blasts while exhibiting low cytotoxicity against CD34+ HSPC in vitro and in humanized mouse models in vivo, suggesting a low risk of myelotoxicity. These results support CD84 as a promising target for AML and T-ALL and provide the foundation for our upcoming first-in-human phase I/II clinical trial using CD84-directed CAR T cell therapy for patients with R/R AML and T-ALL (EudraCT 2024-519966-31-00).

© 2025. The Author(s).

Keywords

• HEMATOPOIETIC STEM; CAR; EXPRESSION; 1ST-IN-HUMAN; PROFILES; CHILDREN