Frontiers in Immunology (May 2024)

Newer generations of multi-target CAR and STAb-T immunotherapeutics: NEXT CART Consortium as a cooperative effort to overcome current limitations

  • Beatriz Martín-Antonio,
  • Belén Blanco,
  • África González-Murillo,
  • Laura Hidalgo,
  • Jordi Minguillón,
  • Gema Pérez-Chacón,
  • Next Generation CART MAD Consortium,
  • Jordi Minguillón,
  • Lucía Fernández,
  • Halin Bareke,
  • Andrés París-Muñoz,
  • Adriana Mañas,
  • Cristina Aguirre-Portolés,
  • Alfonso Navarro-Zapata,
  • Carmen Mestre-Durán,
  • Marta Ibáñez-Navarro,
  • Laura Clares-Villa,
  • Sara Naharro,
  • Antonio Perez-Martinez,
  • Marcos Aldea,
  • María Gaibar,
  • Javier Ruiz-Navarro,
  • Manuel Izquierdo,
  • Juan M. Zapata,
  • África González Murillo,
  • Elena García Sánchez,
  • Jorge García Martínez,
  • Alba Rubio San Simón,
  • Blanca Herrero,
  • Gonzalo García Aguilera,
  • Beatriz Horcajo Morera,
  • Manuel Ramírez Orellana,
  • Belén Blanco-Durango,
  • Anais Jiménez-Reinoso,
  • Rodrigo Lázaro-Gorines,
  • Ivana Zagorac,
  • Antonio Tapia Galisteo,
  • Ángel Ramirez-Fernández,
  • Laura Díez-Alonso,
  • Carmen Dominguez-Alonso,
  • Ainhoa Erce-Llamazares,
  • Oana Hangiu,
  • Laura Rubio Pérez,
  • Marina Gómez Rosel,
  • Alejandro Segura Tudela,
  • Javier Arroyo-Ródena,
  • Luis Álvarez-Vallina,
  • Miguel Ángel Rodríguez Milla,
  • Patricia García Rodríguez,
  • Beatriz Somovilla Crespo,
  • Javier García-Castro,
  • Esperanza Esquinas Tarifa,
  • Juana Serrano-López,
  • Pilar Llamas-Sillero,
  • Beatriz Martin-Antonio

DOI
https://doi.org/10.3389/fimmu.2024.1386856
Journal volume & issue
Vol. 15

Abstract

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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.

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