AUTHOR=Martín-Antonio Beatriz , Blanco Belén , González-Murillo África , Hidalgo Laura , Minguillón Jordi , Pérez-Chacón Gema , Next Generation CART MAD Consortium , Minguillón Jordi , Fernández Lucía , Bareke Halin , París-Muñoz Andrés , Mañas Adriana , Aguirre-Portolés Cristina , Navarro-Zapata Alfonso , Mestre-Durán Carmen , Ibáñez-Navarro Marta , Clares-Villa Laura , Naharro Sara , Perez-Martinez Antonio , Aldea Marcos , Gaibar María , Ruiz-Navarro Javier , Izquierdo Manuel , Zapata Juan M. , Murillo África González , Sánchez Elena García , Martínez Jorge García , Simón Alba Rubio San , Herrero Blanca , Aguilera Gonzalo García , Morera Beatriz Horcajo , Orellana Manuel Ramírez , Blanco-Durango Belén , Jiménez-Reinoso Anais , Lázaro-Gorines Rodrigo , Zagorac Ivana , Galisteo Antonio Tapia , Ramirez-Fernández Ángel , Díez-Alonso Laura , Dominguez-Alonso Carmen , Erce-Llamazares Ainhoa , Hangiu Oana , Pérez Laura Rubio , Rosel Marina Gómez , Tudela Alejandro Segura , Arroyo-Ródena Javier , Álvarez-Vallina Luis , Milla Miguel Ángel Rodríguez , Rodríguez Patricia García , Crespo Beatriz Somovilla , García-Castro Javier , Tarifa Esperanza Esquinas , Serrano-López Juana , Llamas-Sillero Pilar , Martin-Antonio Beatriz TITLE=Newer generations of multi-target CAR and STAb-T immunotherapeutics: NEXT CART Consortium as a cooperative effort to overcome current limitations JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1386856 DOI=10.3389/fimmu.2024.1386856 ISSN=1664-3224 ABSTRACT=

Adoptive T cellular immunotherapies have emerged as relevant approaches for treating cancer patients who have relapsed or become refractory (R/R) to traditional cancer treatments. Chimeric antigen receptor (CAR) T-cell therapy has improved survival in various hematological malignancies. However, significant limitations still impede the widespread adoption of these therapies in most cancers. To advance in this field, six research groups have created the “NEXT Generation CART MAD Consortium” (NEXT CART) in Madrid’s Community, which aims to develop novel cell-based immunotherapies for R/R and poor prognosis cancers. At NEXT CART, various basic and translational research groups and hospitals in Madrid concur to share and synergize their basic expertise in immunotherapy, gene therapy, and immunological synapse, and clinical expertise in pediatric and adult oncology. NEXT CART goal is to develop new cell engineering approaches and treatments for R/R adult and pediatric neoplasms to evaluate in multicenter clinical trials. Here, we discuss the current limitations of T cell-based therapies and introduce our perspective on future developments. Advancement opportunities include developing allogeneic products, optimizing CAR signaling domains, combining cellular immunotherapies, multi-targeting strategies, and improving tumor-infiltrating lymphocytes (TILs)/T cell receptor (TCR) therapy. Furthermore, basic studies aim to identify novel tumor targets, tumor molecules in the tumor microenvironment that impact CAR efficacy, and strategies to enhance the efficiency of the immunological synapse between immune and tumor cells. Our perspective of current cellular immunotherapy underscores the potential of these treatments while acknowledging the existing hurdles that demand innovative solutions to develop their potential for cancer treatment fully.