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Review
. 2021 Feb 8;11(2):238.
doi: 10.3390/biom11020238.

The Application of Nanobody in CAR-T Therapy

Chaolemeng Bao  1 , Quanli Gao  2 , Lin-Lin Li  2   3 , Lu Han  2 , Bingxiang Zhang  1 , Yijin Ding  1 , Zongpei Song  1 , Ruining Zhang  1 , Jishuai Zhang  1 , Xian-Hui Wu  1
Affiliations
Review

The Application of Nanobody in CAR-T Therapy

Chaolemeng Bao et al. Biomolecules. .

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.

Keywords: BCMA; CAR-T; VHH; nanobody.

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Conflict of interest statement

Chaolemeng Bao, Bingxiang Zhang, Yijin Ding, Zongpei Song, Ruining Zhang, Jishuai Zhang, and Xian-Hui Wu have received supports from Shenzhen Pregene Biopharma Co., Ltd. All the other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A brief history of cellular immunotherapy development from bench to bedside. (A) The CAR-T therapies evolved from undefined targets/clinically effective, defined targets/clinically ineffective, to defined targets/clinically effective. (B) The schematic figures of TCR machinery, chimeric TCR machinery, and different generations of CAR-T with the use of scFv.
Figure 2
Figure 2
The mechanism of potential VH-VL mispairing and VH-VH aggregation on high CAR expression levels.
Figure 3
Figure 3
The application of VHH in advanced CAR-T therapies, which include bi-specific/epitopic, cytokine/VHH/VHH-Fc releasing, and UniCAR, etc.
See this image and copyright information in PMC

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