Related Experiment Video
Updated: Sep 4, 2025
In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
Antitumor CAR T-cell Screening Platform: Many Are Called, but Few Are Chosen
Olivier Adotévi1,2, Jeanne Galaine1
1UMR1098, EFS BFC, INSERM, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University of Bourgogne Franche-Comté, Besançon, France.
Abstract:
Treatment with T cells expressing chimeric antigen receptors (CAR) is a promising anticancer therapy. However, this approach has several limitations and has not yet been effectively applied to treat solid tumors. The study by Panowski and colleagues represents the first comparative analysis of multiple single chain fragment variable (scFv)-based anti-CD70 CAR T-cell clones for the development of a clinical product to treat renal cell carcinoma (RCC). Despite the risk of T-cell fratricide due to CD70 expression on T cells, CD70 CAR T cells were produced successfully thanks to the protective CD70 masking phenomenon. Two distinct classes of CAR T cells were identified with different memory phenotypes, activation statuses, and cytotoxic activity. CD70 CAR T cells presented high cytotoxic activity against RCC both in vitro in RCC cell lines and in vivo in patient-derived xenograft mouse models. The off-target effects expected on the lymphoid compartment were confirmed by tissue cross-reactivity staining and in a cynomolgus monkey preclinical model with CD3-CD70 bispecific antibody treatment. The efficacy and the toxicity profile of the lead CD70 CAR T-cell candidate instigated the researchers to proceed with upscaled clinical production. This article emphasizes the influence of the scFv of the CARs on their efficacy:toxicity balance. Ultimately, they successfully managed to develop a highly effective CAR T-cell candidate to treat a solid tumor by an allogeneic approach, thereby overcoming two major hurdles to broaden application of CAR T-cell therapy. See related article by Panowski et al., p. 2610.
Insights
Researchers developed an allogeneic chimeric antigen receptor (CAR) T-cell therapy for renal cell carcinoma (RCC). This CAR T-cell therapy shows high efficacy against solid tumors, overcoming key limitations in current treatments.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) T-cell therapy shows promise for cancer treatment but faces limitations, especially in solid tumors.
- Developing effective CAR T-cell therapies for solid tumors like renal cell carcinoma (RCC) requires overcoming challenges such as T-cell fratricide and off-target effects.
Discussion:
- This study presents the first comparative analysis of single chain fragment variable (scFv)-based anti-CD70 CAR T-cell clones for RCC treatment.
- CD70 CAR T cells were successfully produced, demonstrating potent in vitro and in vivo anti-tumor activity against RCC, despite potential T-cell fratricide.
- The research identified distinct CAR T-cell populations with varying phenotypes and cytotoxic capabilities, highlighting the impact of scFv selection on efficacy and toxicity.
Key Insights:
- CD70 CAR T cells exhibit significant cytotoxic activity against RCC in cell lines and patient-derived xenograft models.
- Off-target effects on the lymphoid compartment were confirmed in preclinical models, emphasizing the need for careful safety assessments.
- The study successfully developed an allogeneic CAR T-cell candidate for solid tumor treatment, addressing major hurdles in CAR T-cell therapy application.
Outlook:
- The lead CD70 CAR T-cell candidate's promising efficacy and toxicity profile support its progression to clinical production.
- This work underscores the critical role of scFv selection in balancing the efficacy and toxicity of CAR T-cell therapies.
- The development of an allogeneic approach for solid tumors broadens the potential application of CAR T-cell therapy in oncology.
