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Updated: Aug 14, 2026
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
The development of chimeric antigen receptor T-cells against CD70 for renal cell carcinoma treatment
Qinghui Xiong1, Haiying Wang2, Qiushuang Shen3
1Shanghai HRAIN Biotechnology Co., Ltd., 1238 Zhangjiang Road, Shanghai, 201203, China. xiongqinghui@dashengbio.com.
Abstract:
In this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-ɑ during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.
Insights
Novel nanobody-based chimeric antigen receptor T (CAR-T) cells targeting CD70 show potent anti-tumor activity against renal cell carcinoma (RCC). These CAR-T cells eradicated tumors in mice, suggesting a promising new therapy for RCC patients.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- CD70 is highly expressed in renal cell carcinoma (RCC) tumors and linked to poorer patient survival.
- Targeting CD70 presents a potential therapeutic strategy for RCC.
Purpose of the Study:
- To develop and evaluate potent chimeric antigen receptor T (CAR-T) cells targeting CD70 for RCC therapy.
- To compare the efficacy of nanobody-based CAR-T cells against traditional single-chain variable fragment (scFv)-based CAR-T cells.
Main Methods:
- Generated CAR-T cells using VHH sequences from novel nanobodies and a human scFv (41D12) targeting CD70.
- Assessed in vitro cytotoxicity against CD70-positive and CD70-negative tumor cells.
- Measured cytokine production (IL-2, IFN-γ, TNF-ɑ) in co-culture experiments.
- Evaluated anti-tumor activity and T cell expansion in a xenograft mouse model.
Main Results:
- Anti-CD70 CAR-T cells effectively eliminated CD70-positive RCC cells in vitro.
- Nanobody-based CAR-T cells showed enhanced cytokine production compared to scFv CAR-T cells.
- CAR-T cells demonstrated significant anti-tumor activity and tumor eradication in a mouse model.
- VHH-based CAR-T cells led to superior T cell expansion and long-lasting tumor-free survival upon re-challenge.
Conclusions:
- Nanobody-derived CD70 CAR-T cells exhibit potent and durable anti-tumor efficacy in preclinical models of RCC.
- These findings support the further development of VHH-based CAR-T cells as a promising therapeutic option for renal cell carcinoma.
