ArticleFrontiers in immunology2021
Bispecific NKG2D-CD3 and NKG2D-CD16 Fusion Proteins as Novel Treatment Option in Advanced Soft Tissue Sarcomas.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 10 citations in OpenAlex.
- The evolution of cellular therapies in sarcoma: Breakthroughs, challenges, and future directions.Human vaccines & immunotherapeutics · 2026Review
- Targeted delivery platforms forFrontiers in pharmacology · 2026Review
- Fc-optimized CD276 antibody enhances NK cell activation against non-small cell lung cancer.Frontiers in immunology · 2025Article
- Induction of NK cell reactivity against acute myeloid leukemia by Fc-optimized CD276 (B7-H3) antibody.Blood cancer journal · 2024Article
- An Fc-modified monoclonal antibody as novel treatment option for pancreatic cancer.Frontiers in immunology · 2024Article
- Targeting NKG2DL with Bispecific NKG2D-CD16 and NKG2D-CD3 Fusion Proteins on Triple-Negative Breast Cancer.International journal of molecular sciences · 2023Article
- Novel NKG2D-directed bispecific antibodies enhance antibody-mediated killing of malignant B cells by NK cells and T cells.Frontiers in immunology · 2023Article
- Immunotherapeutic targeting of activating natural killer cell receptors and their ligands in cancer.Clinical and experimental immunology · 2022Review
- Platelets subvert antitumor efficacy of T cell-recruiting bispecific antibodies.Journal for immunotherapy of cancer · 2022Article
- B7-H3-targeting Fc-optimized antibody for induction of NK cell reactivity against sarcoma.Frontiers in immunology · 2022Article
- Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Soft tissue sarcoma (STS) constitutes a rare group of heterogeneous malignancies. Effective treatment options for most subtypes of STS are still limited. As a result, especially in metastatic disease, prognosis is still dismal. The ligands for the activating immunoreceptor NKG2D (NKG2DL) are commonly expressed in STS, but generally absent in healthy tissues. This provides the rationale for utilization of NKG2DL as targets for immunotherapeutic approaches. We here report on the preclinical characterization of bispecific fusion proteins (BFP) consisting of the extracellular domain of the NKG2D receptor fused to Fab-fragments directed against CD3 (NKG2D-CD3) or CD16 (NKG2D-CD16) for treatment of STS. After characterization of NKG2DL expression patterns on various STS cell lines, we demonstrated that both NKG2D-CD16 and NKG2D-CD3 induce profound T and NK cell reactivity as revealed by analysis of activation, degranulation and secretion of IFNγ as well as granule associated proteins, resulting in potent target cell lysis. In addition, the stimulatory capacity of the constructs to induce T and NK cell activation was analyzed in heavily pretreated STS patients and found to be comparable to healthy donors. Our results emphasize the potential of NKG2D-CD3 and NKG2D-CD16 BFP to target STS even in an advanced disease.
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