Abstract
Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobodies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR structure has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural killer cells, or primary T cells, the resulting nanobody-based CAR-T or CAR-NK cells demonstrate anti-tumor effects both in vitro and in vivo. Interestingly, anti-BCMA CAR-T modulated by a single nanobody or bi-valent nanobody displays comparable clinical effects with that of single-chain variable fragment (scFv)-modulated CAR-T. The application of nanobodies in CAR-T therapy has been well demonstrated from bench to bedside and displays great potential in forming advanced CAR-T for more challenging tasks.
Highlights
In various types of cell therapy, the chimeric antigen receptor (CAR) T cell is the most dominant and active anti-tumor agent in the treatment of cancers, especially in hematological malignancies [2], while limited activity has been shown in solid tumors and several challenges need to be overcome regarding its application [3]
The market has authorized three CAR-T cell products that all target CD19 and rely on scFv derived from the same murine monoclonal antibody, FMC63
Over a dozen targets have been modulated by nanobody-based CARs, which display similar activities to those of scFv
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In various types of cell therapy, the chimeric antigen receptor (CAR) T cell is the most dominant and active anti-tumor agent in the treatment of cancers, especially in hematological malignancies [2], while limited activity has been shown in solid tumors and several challenges need to be overcome regarding its application [3]. The CAR structure is a genetically engineered molecule that direct T cells to attack tumor cells through an antibody–antigen interaction rather than in a major histocompatibility complex (MHC)-dependent manner. Three CAR-T cell-based therapies, tisagenlecleucel (Kymriah), axicabtagene ciloleucel (Yescarta), and brexucabtagene autoleucel (Tecartus), have so far been approved by major regulatory agencies on B-cell precursor acute lymphoblastic leukemia (B-ALL)—that is refractory or in second or later relapse [4], r/r large. All three CAR-T therapies target overexpressed CD19 membrane proteins
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