Discovery and preclinical development of a SdAb-based CAR-T technology for targeting CD33 in AML

Deleted Journal, Journal Year: 2025, Volume and Issue: 33(1), P. 200949 - 200949

Published: Feb. 11, 2025

Chimeric antigen receptor T cell (CAR-T) therapies have revolutionized cancer immunotherapy. Traditional single-chain variable fragments (ScFvs) used as CAR recognition moieties face challenges such high tonic signaling, compromised binding epitopes, and suboptimal affinity. Single-domain antibodies (SdAbs) offer an attractive alternative due to their smaller size, stability, reduced immunogenicity. In this work, we developed SdAb-CAR-T discovery platform integrating generation, characterization, selection of SdAbs based on various properties. This approach was demonstrated by developing CAR-T cells with against CD33, a target for acute myeloid leukemia (AML). We identified diverse affinities ranging from 3.9-115 nM, characterized kinetics epitope recognition. Using SdAb-based second-generation CARs, assessed phenotypes, cytotoxicity cytokine release in vitro, resulting signaling increased production. vivo, exhibited enhanced efficacy at lower doses, xenograft AML mouse model, demonstrating advantages over ScFv-based CD33 cells.

Language: Английский

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CAR T-cell therapy in renal cell carcinoma: opportunities, challenges, and new strategies to overcome

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(6)

Published: April 24, 2025

Language: Английский

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CAR T-cell therapy comes of age: Introductory editorial for the special issue

Seminars in Hematology, Journal Year: 2024, Volume and Issue: 61(5), P. 271 - 272

Published: Oct. 1, 2024

Language: Английский

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