Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Introduction: B7-H6, a tumor-specific immune checkpoint molecule within the B7 family, represents a promising therapeutic target due to its selective overexpression in malignancies and negligible expression in normal tissues.
Method: Here, we developed bispecific antibodies (BsAbs) targeting B7-H6 to redirect T and NK cells against solid tumors. Through phage display, 15 high-affinity B7-H6 monoclonal antibodies were generated.
Results: Two optimized BsAbs, B7-H6M4-OKT3 (T cell-engaging) and B7-H6M4-LC21 (NK cell-engaging), were constructed in and scFv-hFc-scFv format. Both demonstrated nanomolar affinity (EC50: 0.04-1.22 nM) and selective cytotoxicity against B7-H6+ cells (H446, Huh-7, HepG2), while showing minimal cytotoxicity against B7-H6-negative cells (A431). B7-H6M4LC21 exhibited enhanced tumor-killing efficacy (IC50: 5 ng/mL) compared to B7H6M4-OKT3(IC50: 1 ng/mL) when combined with an IL-15/IL-15Ra sushi fusion protein, which augmented NK cell proliferation and cytotoxicity. In H446 xenograft models, both BsAbs suppressed tumor growth in a dose-dependent manner (0.1-20 mg/kg) without significant toxicity. Combination therapy with B7-H6M4-LC21 (10 mg/kg) and B7-H6M18/IL-15/IL-15Ra sushi (0.03 mg/kg) achieved synergistic tumor inhibition (p<0.05), surpassing the efficacy of T cell-based combinations.
Discussion: These findings establish B7-H6-targeted BsAbs combined with cytokine engineering as a viable strategy for treating refractory solid tumors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378318 | PMC |
| http://dx.doi.org/10.3389/fimmu.2025.1625813 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cancer vaccines in hematologic malignancy: A systematic review of the rational and evidence for clinical use.
Best Pract Res Clin Haematol
September 2025
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA; Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, USA.
Immunotherapy, including immune checkpoint blockade, CART cells and bispecific antibodies have resulted in dramatic improvements in outcomes for patients with hematological malignancies, demonstrating the unique potency of the immune system in targeting malignant cells. The development of cancer vaccines aims to evoke an activated effector cell population and a memory response to provide long term immune surveillance to protect from relapse. Developing a potent cancer vaccine relies on identifying appropriate antigen targets, enhancing antigen presentation, and overcoming the immune suppressive milieu of the micro-environment.
View Article and Find Full Text PDFBispecific T-cell engager therapy for multiple myeloma.
Best Pract Res Clin Haematol
September 2025
Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
With upfront use of triplet- and quadruplet-based regimens coupled with autologous stem cell transplant (ASCT) and maintenance lenalidomide, a high proportion of multiple myeloma (MM) patients are achieving deep and durable responses. Yet, myeloma invariably relapses, with refractoriness to one or more drugs at first relapse. This therapeutic gap has been partially filled by T-cell engager (TCE) therapies that have demonstrated remarkable response rates and prolonged remissions in heavily pretreated patients with MM, providing off-the-shelf immunotherapy options leading to the U.
View Article and Find Full Text PDFEvaluation of two IgG-scFv bispecific antibodies for neutralizing Omicron variants of SARS-CoV-2.
J Virol Methods
September 2025
Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico. Electronic address:
Bispecific antibodies (bsAbs) offer an alternative to monoclonal antibody (mAb) cocktails for addressing the loss of efficacy due to the rapid emergence of SARS-CoV-2 mutants. The structure and specificity of the parental antibodies influence the development of a highly neutralizing bsAb. To design an effective bsAb, the recognition of 44 single-chain fragment variable (scFv) antibodies against variants of SARS-CoV-2 was evaluated, along with an assessment of their ability to competitively bind to the receptor-binding domain (RBD) compared to the most potent neutralizing mAbs.
View Article and Find Full Text PDFRelieving platelet inhibition using a novel bi-specific antibody: A novel approach for circumventing the platelet storage lesion.
J Thromb Haemost
September 2025
Blood Research Institute, Versiti, Milwaukee, WI; Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI; Department of Cell biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI. Electronic address:
Background: Human platelets experience structural and functional deterioration during extra-corporeal storage at either room temperature or in the cold, impairing their reactivity and diminishing their hemostatic effectiveness following transfusion. PECAM-1 is an inhibitory receptor on platelets that exerts its inhibitory effects via phosphorylation of tyrosine residues that lie within its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The purpose of this investigation was to attempt to restore platelet reactivity by impairing the inhibitory activity of PECAM-1.
View Article and Find Full Text PDFPurpose Of Review: Autologous stem cell transplantation (ASCT) has long been a cornerstone in the treatment of eligible patients with newly diagnosed multiple myeloma (NDMM). In this review, we analyze the evolving role of ASCT in the contemporary period.
Recent Findings: With the growing integration of modern induction regimens and advanced immunotherapies such as chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies (BsAbs), the traditional paradigm of multiple myeloma treatment is being increasingly challenged.