ArticleScientific reports2023
HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Recent advances in the regulation of CD47 by non-coding RNAs and its therapeutic potential in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- ISX-TWIST1 reprograms CD47-inflammasome signaling to reshape the immune microenvironment in liver cancer.Experimental hematology & oncology · 2026Article
- Targeting the CD47/SIRPα interaction in cancer: opportunities in non-Hodgkin lymphoma.Expert opinion on investigational drugs · 2026Review
- Immunotherapy research for prostate cancer from 2000 to 2024: a bibliometric and visualization analysis.Translational andrology and urology · 2025Article
- Monitoring Response to Combinatorial Immunotherapies by Tracking both T Cells and Natural Killer CellsACS applied materials & interfaces · 2025Article
- Targeting Frequent Efferocytosis in Tumor Microenvironment is a New Direction for Cancer Treatment.Small science · 2025Review
- Preclinical pharmacology characterization of HX009, a novel PD1 x CD47 Bi-specific antibody.Scientific reports · 2024Article
- Article
- Antigen presenting cells in cancer immunity and mediation of immune checkpoint blockade.Clinical & experimental metastasis · 2024Review
- Progress in cancer research on the regulator of phagocytosis CD47, which determines the fate of tumor cells (Review).Oncology letters · 2024Review
- Nanosystem Delivers Senescence Activators and Immunomodulators to Combat Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Discovery of a novel small molecule as CD47/SIRPα and PD-1/PD-L1 dual inhibitor for cancer immunotherapy.Cell communication and signaling : CCS · 2024Article
- A Novel Anti-CD47 Nanobody Tetramer for Cancer Therapy.Antibodies (Basel, Switzerland) · 2024Article
- Targeting CEACAM5-positive solid tumors using NILK-2401, a novel CEACAM5xCD47 κλ bispecific antibody.Frontiers in immunology · 2024Article
- Progress in construction of mouse models to investigate the pathogenesis and immune therapy of human hematological malignancy.Frontiers in immunology · 2023Review
- Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: challenges and opportunities.Frontiers in immunology · 2023Review
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Both PD1/PD-L1 and CD47 blockades have demonstrated limited activity in most subtypes of NHL save NK/T-cell lymphoma. The hemotoxicity with anti-CD47 agents in the clinic has been speculated to account for their limitations. Herein we describe a first-in-class and rationally designed bispecific antibody (BsAb), HX009, targeting PD1 and CD47 but with weakened CD47 binding, which selectively hones the BsAb for tumor microenvironment through PD1 interaction, potentially reducing toxicity. In vitro characterization confirmed: (1) Both receptor binding/ligand blockade, with lowered CD47 affinity; (2) functional PD1/CD47 blockades by reporter assays; (3) T-cell activation in Staphylococcal-enterotoxin-B-pretreated PBMC and mixed-lymphocyte-reaction. In vivo modeling demonstrated antitumor activity in Raji-B and Karpass-229-T xenograft lymphomas. In the humanized mouse syngeneic A20 B-lymphoma (huCD47-A20) HuGEMM model, which has quadruple knocked-in hPD1xhPD-L1xhCD47xhSIRPα genes and an intact autologous immune-system, a contribution of effect is demonstrated for each targeted biologic (HX008 targeting PD1 and SIRPα-Fc targeting CD47), which is clearly augmented by the dual targeting with HX009. Lastly, the expression of the immune-checkpoints PD-L1/L2 and CD47 seemed co-regulated among a panel of lymphoma-derived-xenografts, where HX009 maybe more effective in those with upregulated CD47. Our data warrants HX009's further clinical development for treating NHLs.
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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.