ArticleFrontiers in immunology2023
T-cells engineered with a novel VHH-based chimeric antigen receptor against CD19 exhibit comparable tumoricidal efficacy to their FMC63-based counterparts.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials.Frontiers in pharmacology · 2023Pooled it
- Antibody format matters: A comparative analysis of VHH and scFv domains reveals superior in vivo CAR T cell function with VHH domains.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- EF-1α-driven nanobody-based CD19-redirected CAR-T cells retain the antitumor efficacy, antigen-driven expansion, and cytokine secretion of CMV-driven counterparts.Molecular and cellular biochemistry · 2026Article
- Nanobody-based targeted cancer therapy and immunotherapy: fear not the future.Acta pharmacologica Sinica · 2026Review
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Characterization of a Phage Display-Selected scFv Against Neuropilin 1 (NRP1) Isolated from a Naïve Human Library.Molecular biotechnology · 2026Article
- CAR-T cell immunotherapy in rhabdomyosarcoma.Journal of translational medicine · 2026Review
- Article
- Application of nanobody‑based CAR‑T in tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Preventing secondary primary malignancies (SPMs) in CAR-T cell therapy through site-specific transgene integration into genomic safe harbors (GSHs).Journal of translational medicine · 2025Review
- Nanobodies and their derivatives: pioneering the future of cancer immunotherapy.Cell communication and signaling : CCS · 2025Review
- Engineered SH3-Derived Sherpabodies Function as a Modular Platform for Targeted T-cell Immunotherapy.Cancer research · 2025Article
- Nanobody-enhanced chimeric antigen receptor T-cell therapy: overcoming barriers in solid tumors with VHH and VNAR-based constructs.Biomarker research · 2025Review
- Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines.Molecular cancer · 2025Review
- Mechanisms of antigen-dependent resistance to chimeric antigen receptor (CAR)-T cell therapies.Cancer cell international · 2025Review
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- Challenges in the preclinical design and assessment of CAR-T cells.Frontiers in immunology · 2025Review
- VHH-based CAR-T cells targeting Claudin 18.2 show high efficacy in pancreatic cancer models.Frontiers in immunology · 2025Article
- Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.Journal of hematology & oncology · 2024Review
- Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.Journal of nanobiotechnology · 2024Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Chimeric antigen receptor (CAR)-T cell therapy has established itself as a potent therapeutic option for certain patients with relapsed/refractory (R/R) hematologic malignancies. To date, four CD19-redirected CAR-T cell products have been granted the United States Food and Drug Administration (FDA) approval for medical use. However, all of these products are equipped with a single-chain fragment variable (scFv) as their targeting domains. Camelid single-domain antibodies (VHH or nanobody) can also be used as alternatives to scFvs. In this study, we developed VHH-based CD19-redirected CAR-Ts, and compared them with their FMC63 scFv-based counterpart. Methods: Human primary T cells were transduced to express a second-generation 4-1BB-CD3ζ-based CAR construct whose targeting domain was based on a CD19-specific VHH. The expansion rate, cytotoxicity, and secretion of proinflammatory cytokines (IFN-γ, IL-2, and TNF-α) of the developed CAR-Ts were assessed and compared with their FMC63 scFv-based counterpart as they were co-cultured with CD19-positive (Raji and Ramos) and CD19-negative (K562) cell lines. Results: VHH-CAR-Ts showed an expansion rate comparable to that of the scFv-CAR-Ts. In terms of cytotoxicity, VHH-CAR-Ts mediated cytolytic reactions against CD19-positive cell lines, comparable to those of their scFv-based counterparts. Moreover, both VHH-CAR-Ts and scFv-CAR-Ts secreted remarkably higher and similar levels of IFN-γ, IL-2, and TNF-α upon co-cultivation with Ramos and Raji cell lines compared with while cultured alone or co-cultured with K562 cells. Conclusion: Our results demonstrated that our VHH-CAR-Ts could mediate CD19-dependent tumoricidal reactions as potently as their scFv-based counterparts. Moreover, VHHs could be applied as the targeting domains of CAR constructs to overcome the issues associated with the use of scFvs in CAR-T therapies.
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