ArticleJournal of nanobiotechnology2022
Combining a nanoparticle-mediated immunoradiotherapy with dual blockade of LAG3 and TIGIT improves the treatment efficacy in anti-PD1 resistant lung cancer.
Article in Journal of nanobiotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Efficacy of PD-1/PD-L1 and LAG-3 immune checkpoint inhibitors in the treatment of patients with solid tumor.Frontiers in immunology · 2026Pooled it
- Tumor Treating Fields (TTFields) sensitize anti-PD1-resistant lung tumors to PD1 blockade and remodel myeloid and lymphoid states.Research square · 2026Article
- Timing matters: how mechanism-guided sequencing shapes the efficacy of radiotherapy-immunotherapy combinations : A systematic review.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Review
- CT26.MtC3, a new preclinical model to investigate immune resistance in metastatic colorectal cancer.Cancer cell international · 2026Article
- Nanomaterial-Enabled Modulation of Tumor-Associated Macrophages and Dendritic Cells to Enhance Cancer Immunotherapy.Nanomaterials (Basel, Switzerland) · 2026Review
- Overcoming resistance to anti-PD-1/PD-L1 therapy in cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- The radioenhancer NBTXR3: bridging physics and biology to improve radiotherapy outcomes and prime anti-tumor immunity.Journal of experimental & clinical cancer research : CR · 2025Review
- Next-generation immunotherapies for head and neck squamous cell carcinoma: targeting novel immune checkpoints.Annals of medicine · 2025Review
- LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with Radiotherapy.Current oncology (Toronto, Ont.) · 2025Review
- Research trends and highlights in PD-1/PD-L1 inhibitor immunotherapy in lung cancer: a bibliometric analysis.Discover oncology · 2025Article
- Overcoming resistance to immune checkpoint inhibitor in non-small cell lung cancer: the promise of combination therapy.Frontiers in immunology · 2025Review
- Superior antitumor immune response achieved with proton over photon immunoradiotherapy is amplified by the nanoradioenhancer NBTXR3.Journal of nanobiotechnology · 2024Article
- Implementation of a High-Accuracy Targeted Gene Expression Panel for Clinical Care.The Journal of molecular diagnostics : JMD · 2024Article
- LAG-3 : recent developments in combinational therapies in cancer.Cancer science · 2024Review
- Regulatory mechanisms of PD-1/PD-L1 in cancers.Molecular cancer · 2024Review
- Article
- Dual immunotherapy in advanced or metastatic non-small cell lung cancer: A network meta-analysis.Heliyon · 2024Article
- Radiotherapy-activated NBTXR3 nanoparticles promote ferroptosis through induction of lysosomal membrane permeabilization.Journal of experimental & clinical cancer research : CR · 2024Article
- Application of nano-radiosensitizers in non-small cell lung cancer.Frontiers in oncology · 2024Review
- Advancing non-small cell lung cancer treatment: the power of combination immunotherapies.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWhile improvements in immunoradiotherapy have significantly improved outcomes for cancer patients, this treatment approach has nevertheless proven ineffective at controlling the majority of malignancies. One of the mechanisms of resistance to immunoradiotherapy is that immune cells may be suppressed via the myriad of different immune checkpoint receptors. Therefore, simultaneous blockade of multiple immune checkpoint receptors may enhance the treatment efficacy of immunoradiotherapy.
methodsWe combined NBTXR3-enhanced localized radiation with the simultaneous blockade of three different checkpoint receptors: PD1, LAG3, and TIGIT, and tested the treatment efficacy in an anti-PD1-resistant lung cancer model in mice. 129 Sv/Ev mice were inoculated with fifty thousand αPD1-resistant 344SQR cells in the right leg on day 0 to establish primary tumors and with the same number of cells in the left leg on day 4 to establish the secondary tumors. NBTXR3 was intratumorally injected into the primary tumors on day 7, which were irradiated with 12 Gy on days 8, 9, and 10. Anti-PD1 (200 µg), αLAG3 (200 µg), and αTIGIT (200 µg) were given to mice by intraperitoneal injections on days 5, 8, 11, 14, 21, 28, 35, and 42.
resultsThis nanoparticle-mediated combination therapy is effective at controlling the growth of irradiated and distant unirradiated tumors, enhancing animal survival, and is the only one that led to the destruction of both tumors in approximately 30% of the treated mice. Corresponding with this improved response is robust activation of the immune response, as manifested by increased numbers of immune cells along with a transcriptional signature of both innate and adaptive immunity within the tumor. Furthermore, mice treated with this combinatorial therapy display immunological memory response when rechallenged by the same cancer cells, preventing tumor engraftment.
conclusionOur results strongly attest to the efficacy and validity of combining nanoparticle-enhanced radiotherapy and simultaneous blockade of multiple immune checkpoint receptors and provide a pre-clinical rationale for investigating its translation into human patients.
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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.