ArticleJournal of experimental & clinical cancer research : CR2019
Development of a human immuno-oncology therapeutic agent targeting HER2: targeted delivery of granzyme B.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 25 citations in OpenAlex.
- Fusion Protein Technology to Enhance Pharmacological Properties of L-Asparaginases.Biomolecules · 2026Review
- BAFF-based trifunctional T-cell engagers trigger robust tumor immunity against B-cell malignancies.Protein & cell · 2025Article
- EGFR-targeting RNase A-cetuximab antibody-drug conjugate induces ROS-mediated apoptosis to overcome drug resistance in KRAS mutant cancer cells.Scientific reports · 2025Article
- The pro-tumorigenic roles of granzyme B: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
- GrB-Fc-KS49, an anti-EMP2 granzyme B fusion protein therapeutic alters immune cell infiltration and suppresses breast cancer growth.Journal for immunotherapy of cancer · 2024Article
- Modeling antibody drug conjugate potential using a granzyme B antibody fusion protein.BMC biology · 2024Article
- Serpin B9 is Highly Expressed in Lung Adenocarcinoma and is Associated with Progression-Free Survival.Journal of inflammation research · 2024Article
- Engineered antibody fusion proteins for targeted disease therapy.Trends in pharmacological sciences · 2021Review
- Recombinant immunotoxins development for HER2-based targeted cancer therapies.Cancer cell international · 2021Review
- Therapeutic efficacy and safety of a human fusion construct targeting the TWEAK receptor Fn14 and containing a modified granzyme B.Journal for immunotherapy of cancer · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundImmunotherapeutic approaches designed to augment T and B cell mediated killing of tumor cells has met with clinical success in recent years suggesting tremendous potential for treatment in a broad spectrum of tumor types. After complex recognition of target cells by T and B cells, delivery of the serine protease granzyme B (GrB) to tumor cells comprises the cytotoxic insult resulting in a well-characterized, multimodal apoptotic cascade.
methodsWe designed a recombinant fusion construct, GrB-Fc-4D5, composed of a humanized anti-HER2 scFv fused to active GrB for recognition of tumor cells and internal delivery of GrB, simulating T and B cell therapy. We assessed the construct's antigen-binding specificity and GrB enzymatic activity, as well as in vitro cytotoxicity and internalization into target and control cells. We also assessed pharmacokinetic and toxicology parameters in vivo.
resultsGrB-Fc-4D5 was highly cytotoxic to Her2 positive cells such as SKBR3, MCF7 and MDA-MB-231 with IC
conclusionGrB-Fc-4D5 shows excellent, specific cytotoxicity and demonstrates no significant toxicity in normal, antigen-negative murine models. This construct constitutes a novel approach against HER2-expressing tumors and is an excellent candidate for further development.
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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.