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Review
. 2024 May 8:15:1386856.
doi: 10.3389/fimmu.2024.1386856. eCollection 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  1 , Belén Blanco  2 , África González-Murillo  3 , Laura Hidalgo  4 , Jordi Minguillón  5 , Gema Pérez-Chacón  6 ; Next Generation CART MAD Consortium
Collaborators, Affiliations
Review

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

Beatriz Martín-Antonio et al. Front Immunol. .

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.

Keywords: CAR-T cells; NK cells; TCR therapy; TILs; cancer; immunological synapse.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Immunological synapse features of TCRs, CAR-T cells, and STAb-T cells: The main differences in the IS of TCRs, CAR-T cells, and STAb-T cells are shown. These differences could guide new lines of research to improve CAR-T cells’ IS formation.
See this image and copyright information in PMC

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