ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Immunotherapeutic HCW9218 augments anti-tumor activity of chemotherapy via NK cell-mediated reduction of therapy-induced senescent cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Senogenic-senolytic treatment strategies enhance tumor control and can improve survival in murine cancer models: a systematic review.BMC cancer · 2026Pooled it
- Mechanistic insights into taxane-induced psychiatric adverse events: a global pharmacovigilance and experimental investigation.Molecular psychiatry · 2026Article
- mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synergistic interactions and optimal sequencing of chemotherapy and immunotherapy in cancer treatment.Cancer chemotherapy and pharmacology · 2026Review
- Research progress on the spatiotemporal dynamics of therapy-induced senescence in remodeling the tumor microenvironment.Frontiers in immunology · 2026Review
- TGF-βRII/IL-15 immunotherapeutic complex targets exhausted CD8Journal for immunotherapy of cancer · 2025Article
- Review
- Persistent accumulation of therapy-induced senescent cells: an obstacle to long-term cancer treatment efficacy.International journal of oral science · 2025Review
- Recent advances in engineered exosome-based therapies for ocular vascular disease.Journal of nanobiotechnology · 2025Review
- Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.Cancer communications (London, England) · 2024Review
- Stimulating the Antitumor Immune Response Using Immunocytokines: A Preclinical and Clinical Overview.Pharmaceutics · 2024Review
- Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024Review
- Impact and potential value of immunosenescence on solid gastrointestinal tumors.Frontiers in immunology · 2024Review
- The Cross Talk between Cellular Senescence and Melanoma: From Molecular Pathogenesis to Target Therapies.Cancers · 2023Review
- Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice.Aging cell · 2023Article
- The Potential of Senescence as a Target for Developing Anticancer Therapy.International journal of molecular sciences · 2023Review
- Potentiation of natural killer cells to overcome cancer resistance to NK cell-based therapy and to enhance antibody-based immunotherapy.Frontiers in immunology · 2023Review
- A novel interleukin-2-based fusion molecule, HCW9302, differentially promotes regulatory T cell expansion to treat atherosclerosis in mice.Frontiers in immunology · 2023Article
- Research progress of interleukin-15 in cancer immunotherapy.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapy induced senescence (TIS) in tumors and TIS cancer cells secrete proinflammatory senescence-associated secretory phenotype (SASP) factors. SASP factors promote TIS cancer cells to re-enter the growth cycle with stemness characteristics, resulting in chemo-resistance and disease relapse. Herein, we show that the immunotherapeutic HCW9218, comprising transforming growth factor-β (TGF-β) receptor II and interleukin (IL)-15/IL-15 receptor α domains, enhances metabolic and cytotoxic activities of immune cells and reduces TIS tumor cells in vivo to improve the efficacy of docetaxel and gemcitabine plus nab-paclitaxel against B16F10 melanoma and SW1990 pancreatic tumors, respectively. Mechanistically, HCW9218 treatment reduces the immunosuppressive tumor microenvironment and enhances immune cell infiltration and cytotoxicity in the tumors to eliminate TIS cancer cells. Immuno-depletion analysis suggests that HCW9218-activated natural killer cells play a pivotal role in TIS cancer cell removal. HCW9218 treatment following docetaxel chemotherapy further enhances efficacy of tumor antigen-specific and anti-programmed death-ligand 1 (PD-L1) antibodies in B16F10 tumor-bearing mice. We also show that HCW9218 treatment decreases TIS cells and lowers SASP factors in off-target tissues caused by chemotherapy of tumor-bearing mice. Collectively, HCW9218 has the potential to significantly enhance anti-tumor efficacy of chemotherapy, therapeutic antibodies, and checkpoint blockade by eliminating TIS cancer cells while reducing TIS-mediated proinflammatory side effects in normal tissues.
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