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Stornaiuolo A, Valentinis B, Sirini C, et al. Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer. Hum Gene Ther. 2021;32(13):744-760doi: 10.1089/hum.2020.216.
Stornaiuolo, A., Valentinis, B., Sirini, C., Scavullo, C., Asperti, C., Zhou, D., Martinez De La Torre, Y., Corna, S., Casucci, M., Porcellini, S., & Traversari, C. (2021). Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer. Human gene therapy, 32(13), 744-760. https://doi.org/10.1089/hum.2020.216
Stornaiuolo, Anna, et al. "Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer." Human gene therapy vol. 32,13 (2021): 744-760. doi: https://doi.org/10.1089/hum.2020.216
Stornaiuolo A, Valentinis B, Sirini C, Scavullo C, Asperti C, Zhou D, Martinez De La Torre Y, Corna S, Casucci M, Porcellini S, Traversari C. Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer. Hum Gene Ther. 2021 Jul;32(13):744-760. doi: 10.1089/hum.2020.216. Epub 2021 May 05. PMID: 33554732; PMCID: PMC8312023.
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Hum Gene Ther. 2021 Jul;32(13):744-760. doi: 10.1089/hum.2020.216. Epub 2021 May 05.

Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer.

Human gene therapy

Anna Stornaiuolo, Barbara Valentinis, Camilla Sirini, Cinzia Scavullo, Claudia Asperti, Dan Zhou, Yeny Martinez De La Torre, Stefano Corna, Monica Casucci, Simona Porcellini, Catia Traversari

Affiliations

  1. Research Department, AGC Biologics SpA (Formerly MolMed SpA), Milan, Italy.
  2. Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCSS San Raffaele Scientific Institute, Milan, Italy; and.
  3. Vita-Salute San Raffaele University, Milan, Italy.

PMID: 33554732 PMCID: PMC8312023 DOI: 10.1089/hum.2020.216

Abstract

Effectiveness of adoptively transferred chimeric antigen receptor (CAR) T cells strongly depends on the quality of CAR-mediated interaction of the effector cells with the target antigen on tumor cells. A major role in this interaction is played by the affinity of the single-chain variable fragment (scFv) for the antigen, and by the CAR design. In particular, the spacer domain may impact on the CAR T cell function by affecting the length and flexibility of the resulting CAR. This study addresses the need to improve the manufacturing process and the antitumor activity of CD44v6-specific CAR T cells by defining the optimal structure of a spacer region derived from the extracellular domain of the human low-affinity nerve growth factor receptor (LNGFR). We tailored the LNGFR spacer to modulate CAR length to efficiently recognize distal or proximal epitopes and to allow selection of transduced CAR T cells by the use of clinical-grade validated manufacturing systems. The different LNGFR spacers investigated in this study are responsible for the generation of CAR T cells with a different memory phenotype, which is mainly related to the level of CAR expression and the extent of the associated tonic signaling. In particular, the CD44v6-NWN2.CAR T cells are enriched in central memory cells and show improved

Keywords: CAR T; CD44v6; adoptive cell therapy; solid tumor; spacer

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