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Updated: Feb 11, 2026
Production of Human CRISPR-Engineered CAR-T Cells
Published on: March 15, 2021
CD44v6 as innovative sarcoma target for CAR-redirected CIK cells
V Leuci1,2, G M Casucci3, G Grignani2
1Department of Oncology, University of Torino, Torino, Italy.
Abstract:
Purpose of our study was to explore a new immunotherapy for high grade soft tissue sarcomas (STS) based on cytokine-induced killer cells (CIK) redirected with a chimeric antigen receptor (CAR) against the tumor-promoting antigen CD44v6. We aimed at generating bipotential killers, combining the CAR specificity with the intrinsic tumor-killing ability of CIK cells (CAR+.CIK). We set a patient-derived experimental platform. CAR+.CIK were generated by transduction of CIK precursors with a lentiviral vector encoding for anti-CD44v6-CAR. CAR+.CIK were characterized and assessed in vitro against multiple histotypes of patient-derived STS. The anti-sarcoma activity of CAR+.CIK was confirmed in a STS xenograft model. CD44v6 was expressed by 40% (11/27) of patient-derived STS. CAR+.CIK were efficiently expanded from patients (n = 12) and killed multiple histotypes of STS (including autologous targets, n = 4). The killing activity was significantly higher compared with unmodified CIK, especially at low effector/target (E/T) ratios: 98% vs 82% (E/T = 10:1) and 68% vs 26% (1:4), (p<0.0001). Specificity of tumor killing was confirmed by blocking with anti-CD44v6 antibody. CAR+.CIK produced higher amounts of IL6 and IFN-γ compared to control CIK. CAR+.CIK were highly active in mice bearing subcutaneous STS xenografts, with significant delay of tumor growth (p<0.0001) without toxicities. We report first evidence of CAR+.CIK's activity against high grade STS and propose CD44v6 as an innovative target in this setting. CIK are a valuable platform for the translation of CAR-based strategies to challenging field of solid tumors. Our findings support the exploration of CAR+.CIK in clinical trials against high grade STS.
Insights
This study introduces a novel immunotherapy using chimeric antigen receptor (CAR)-engineered cytokine-induced killer (CIK) cells targeting CD44v6 for high-grade soft tissue sarcomas (STS). CAR+ CIK cells demonstrated potent anti-sarcoma activity in vitro and in vivo, suggesting potential for clinical trials.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- High-grade soft tissue sarcomas (STS) present a significant therapeutic challenge.
- Current treatments for STS have limitations, necessitating novel approaches.
- Chimeric antigen receptor (CAR) technology offers a promising avenue for targeted cancer immunotherapy.
Purpose of the Study:
- To explore a new immunotherapy for high-grade STS using CAR-redirected cytokine-induced killer (CIK) cells targeting the CD44v6 antigen.
- To generate and evaluate CAR-positive CIK (CAR+ CIK) cells, combining CAR specificity with CIK cell effector functions.
- To establish a patient-derived experimental platform for assessing CAR+ CIK efficacy against STS.
Main Methods:
- Generation of CAR+ CIK cells via lentiviral transduction of CIK precursors with anti-CD44v6-CAR.
- In vitro characterization and assessment of CAR+ CIK cell activity against patient-derived STS.
- Evaluation of CAR+ CIK cell anti-sarcoma efficacy in a murine STS xenograft model.
Main Results:
- CD44v6 expression was detected in 40% of patient-derived STS.
- CAR+ CIK cells were efficiently expanded from patients and demonstrated potent killing of multiple STS histotypes, including autologous targets.
- CAR+ CIK cells exhibited significantly enhanced killing activity compared to unmodified CIK cells, particularly at low effector/target ratios.
- In vivo studies showed significant delay in STS xenograft tumor growth with CAR+ CIK treatment without observed toxicities.
- CAR+ CIK cells produced higher levels of IL-6 and IFN-γ compared to control CIK cells.
Conclusions:
- First evidence of CAR+ CIK cell activity against high-grade STS.
- CD44v6 is proposed as an innovative therapeutic target for STS.
- CIK cells serve as a valuable platform for translating CAR-based strategies to solid tumors.
- CAR+ CIK cells warrant further exploration in clinical trials for high-grade STS.
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