Abstract
Chimeric antigen receptor T (CAR-T) cell therapy achieved extraordinary achievements results in antitumor treatments, especially against hematological malignancies, where it leads to remarkable, long-term antineoplastic effects with higher target specificity. Nevertheless, some limitations persist in autologous CAR-T cell therapy, such as high costs, long manufacturing periods, and restricted cell sources. The development of a universal CAR-T (UCAR-T) cell therapy is an attractive breakthrough point that may overcome most of these drawbacks. Here, we review the progress and challenges in CAR-T cell therapy, especially focusing on comprehensive comparison in UCAR-T cell therapy to original CAR-T cell therapy. Furthermore, we summarize the developments and concerns about the safety and efficiency of UCAR-T cell therapy. Finally, we address other immune cells, which might be promising candidates as a complement for UCAR-T cells. Through a detailed overview, we describe the current landscape and explore the prospect of UCAR-T cell therapy.
Highlights
With the vigorous development of cellular immunotherapy and the blowout of new clinical trials, various emerging cellular drugs have brought about a qualitative leap in the antineoplastic field
Given the complexity of dual signal controlled by T-cell receptor (TCR) and chimeric antigen receptors (CARs), the elimination of graft versus host disease (GVHD) by disrupting TCR has become a strategy adopted by most allogeneic CAR T-cell researchers
transcription activator-like nucleases (TALENs) is most adopted by Allogene Therapeutics, and CRISPR/Cas9 offers even greater flexibility, maneuverability, and relative accuracy, opening the possibility of multiple gene editing (Figure 2)
Summary
With the vigorous development of cellular immunotherapy and the blowout of new clinical trials, various emerging cellular drugs have brought about a qualitative leap in the antineoplastic field. A retrospective study compared 14 patients receiving allogeneic CAR-T cells (3 donor-derived and 11 recipient-derived) after HSCT with 17 patients receiving autologous CAR-T cells [22]. Given the complexity of dual signal controlled by TCR and CAR, the elimination of GVHD by disrupting TCR has become a strategy adopted by most allogeneic CAR T-cell researchers This strategy of transplant bridging to a recipient or donorderived CAR-T cell therapy is stranded in one-to-one correspondence, far from the envisaged one-to-many universalization. There have been more than hundreds of preclinical and clinical trials of allogeneic CAR-T cell therapy worldwide [18, 25] The majority of these are applied to hematological malignancies, where the most popular target is CD19, and other classic targets, including CD20, CD22, and BCMA.
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