ArticleCancer immunology, immunotherapy : CII2022
Engineering a natural ligand-based CAR: directed evolution of the stress-receptor NKp30.
Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- B7-H6/NKp30 Axis in Melanoma: Translational Rationale, Evidence Gaps, and Therapeutic Considerations.Biomolecules · 2026Review
- NKG2A+ NK cell cytotoxicity of Epstein-Barr virus infected B cells is mediated through the NKG2D and NKp30 activating receptors.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Ligand-Based CAR-T Cells Targeting EGFR Exhibit Favorable Antitumor Effects Against Gynecologic Malignancies.Cancer science · 2025Article
- NKp30: A Key Membrane Molecule in the Fight Against Cancer and Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Mechanisms of antigen-dependent resistance to chimeric antigen receptor (CAR)-T cell therapies.Cancer cell international · 2025Review
- Ligand-based, piggyBac-engineered CAR-T cells targeting EGFR are safe and effective against non-small cell lung cancers.Molecular therapy oncolytics · 2023Article
- Evolution and synthetic biology.Current opinion in microbiology · 2023Review
- SECTM1-based CAR T cells enriched with CD7-low/negative subsets exhibit efficacy in CD7-positive malignancies.Blood advances · 2023Article
- Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia.Frontiers in immunology · 2023Article
- Toward high-throughput engineering techniques for improving CAR intracellular signaling domains.Frontiers in bioengineering and biotechnology · 2023Article
- Superkine IL-2 and IL-33 Armored CAR T Cells Reshape the Tumor Microenvironment and Reduce Growth of Multiple Solid Tumors.Cancer immunology research · 2022Article
- A Protease Activatable Interleukin-2 Fusion Protein Engenders Antitumor Immune Responses by Interferon Gamma-Dependent and Interferon Gamma-Independent Mechanisms.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Article
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
B7H6, a stress-induced ligand which binds to the NK cell receptor NKp30, has recently emerged as a promising candidate for immunotherapy due to its tumor-specific expression on a broad array of human tumors. NKp30 can function as a chimeric antigen receptor (CAR) extracellular domain but exhibits weak binding with a fast on and off rate to B7H6 compared to the TZ47 anti-B7H6 single-chain variable fragment (scFv). Here, directed evolution using yeast display was employed to isolate novel NKp30 variants that bind to B7H6 with higher affinity compared to the native receptor but retain its fast association and dissociation profile. Two variants, CC3 and CC5, were selected for further characterization and were expressed as soluble Fc-fusion proteins and CARs containing CD28 and CD3ς intracellular domains. We observed that Fc-fusion protein forms of NKp30 and its variants were better able to bind tumor cells expressing low levels of B7H6 than TZ47, and that the novel variants generally exhibited improved in vitro tumor cell killing relative to NKp30. Interestingly, CAR T cells expressing the engineered variants produced unique cytokine signatures in response to multiple tumor types expressing B7H6 compared to both NKp30 and TZ47. These findings suggest that natural CAR receptors can be fine-tuned to produce more desirable signaling outputs while maintaining evolutionary advantages in ligand recognition relative to scFvs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.