Daily Respiratory Research Analysis
Analyzed 218 papers and selected 3 impactful papers.
Summary
A phase 3 randomized trial showed that adding the bispecific antibody ivonescimab to chemotherapy improved overall survival in EGFR-variant nonsquamous NSCLC after prior EGFR-TKI therapy. A mechanistic ACS Nano study revealed that disease-specific protein coronas on inhaled nanoplastics can reprogram tumor immunity and accelerate lung adenocarcinoma growth. U.S. national influenza surveillance reported predominance of drifted A(H3N2) subclade K viruses with modest but significant vaccine effectiveness and preserved antiviral susceptibility.
Research Themes
- Targeted and immunotherapy advances in lung cancer
- Environmental nanoplastics and tumor-immune interactions
- Seasonal influenza surveillance and vaccine effectiveness
Selected Articles
1. Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant Non-Small Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial.
In a double-blind phase 3 trial (N=322), ivonescimab plus pemetrexed/carboplatin improved overall survival versus chemotherapy alone in EGFR-variant nonsquamous NSCLC after EGFR-TKI therapy (median 16.8 vs 14.1 months; HR 0.74). Thirty‑month survival increased by ~11 percentage points, with manageable toxicity.
Impact: This trial demonstrates a statistically significant OS benefit with a first-in-class PD‑1/VEGF bispecific antibody in a high-need post‑EGFR‑TKI setting, potentially redefining subsequent-line standards.
Clinical Implications: For EGFR-variant nonsquamous NSCLC progressing after EGFR-TKIs, ivonescimab plus pemetrexed/carboplatin is a survival-improving option with acceptable safety and should be considered where available.
Key Findings
- Median OS improved from 14.1 to 16.8 months (HR 0.74; 95% CI 0.58–0.95; P=.02).
- Estimated 30‑month survival was 29.1% with ivonescimab vs 18.4% with placebo.
- Grade ≥3 treatment-emergent adverse events occurred in 67.1% vs 54.7%.
Methodological Strengths
- Randomized, double-blind, placebo-controlled phase 3 design across 55 sites
- Hierarchical testing with independent radiology review for PFS, adequate follow-up (median 32.5 months)
Limitations
- Conducted exclusively in China, which may limit generalizability
- Absolute OS gain of 2.7 months; higher grade ≥3 AEs in the ivonescimab arm
Future Directions: External validation in diverse populations, biomarker refinement (PD‑L1, VEGF axis), and comparative effectiveness versus other post‑TKI regimens are warranted.
IMPORTANCE: Patients with epidermal growth factor receptor (EGFR) gene variant nonsquamous non-small cell lung cancer (NSCLC) who have disease progression after prior EGFR tyrosine kinase inhibitor (TKI) therapy have limited treatment options, creating a need for more effective subsequent therapies. OBJECTIVE: To provide final overall results of a trial assessing whether adding ivonescimab (a bispecific antibody targeting programmed cell death protein 1 and vascular endothelial growth factor) to chemotherapy improves overall survival in this population. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled phase 3 trial conducted at 55 sites in China. From January 25 to November 2, 2022, a total of 322 adult patients with locally advanced or metastatic EGFR-variant nonsquamous NSCLC who had received prior EGFR-TKI therapy were enrolled. The data cutoff date was April 12, 2025. INTERVENTIONS: Patients were randomized 1:1 to receive ivonescimab (20 mg/kg; n = 161) or placebo (n = 161) plus chemotherapy with pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy. MAIN OUTCOMES AND MEASURES: This final results report focuses on overall survival, the key secondary end point, tested in a hierarchical manner (the primary end point was progression-free survival assessed by an independent radiology review committee). RESULTS: The 322 enrolled patients had a median age of 59.4 years, and 51.6% were female. During a median follow-up of 32.5 months, ivonescimab plus chemotherapy improved overall survival compared with chemotherapy alone (median survival, 16.8 months vs 14.1 months; stratified hazard ratio, 0.74; 95% CI, 0.58-0.95; P = .02). The absolute difference in median overall survival was 2.7 months. Estimated 30-month survival rates were 29.1% (95% CI, 22.1%-36.4%) with ivonescimab and 18.4% (95% CI, 12.8%-24.8%) with placebo. Grade 3 or higher treatment-emergent adverse events occurred in 67.1% and 54.7% of patients receiving ivonescimab and placebo, respectively. CONCLUSIONS AND RELEVANCE: Ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in overall survival with an acceptable safety profile in patients with EGFR-variant NSCLC after EGFR-TKI therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05184712.
2. Personalized Pathogenic Nanoplastic Coronas Orchestrate Efferocytosis-Driven Immune Evasion in Lung Adenocarcinoma.
In mouse lung adenocarcinoma models, inhaled PET nanoplastics accelerated tumor growth. Proteomics of patient BALF–derived coronas identified lysozyme as an enriched component whose corona binding remodeled LYZ and activated TLR4–PGRN–LXRα signaling, enhancing efferocytosis and M2 polarization while suppressing CD8+ T-cell responses.
Impact: This work uncovers a previously unrecognized mechanism linking environmental nanoplastic exposure to tumor immune evasion via disease-specific protein coronas, providing actionable targets (e.g., TLR4, LXRα) for intervention.
Clinical Implications: While preclinical, findings suggest mitigating NP exposure and targeting TLR4–PGRN–LXRα signaling or efferocytosis could complement lung cancer immunotherapy, especially in polluted environments.
Key Findings
- Inhaled PET nanoplastics accelerated tumor growth in lung adenocarcinoma mouse models.
- BALF-derived coronas from patients selectively enriched lysozyme (LYZ), correlating with stage and metastasis.
- Corona-bound LYZ activated TLR4–PGRN–LXRα signaling, increasing efferocytosis and M2 polarization while reducing CD8+ T-cell responses.
Methodological Strengths
- Integrated in vivo tumor models with patient-derived proteomic coronagraphy
- Mechanistic dissection of signaling (TLR4–PGRN–LXRα) and functional immune consequences
Limitations
- Human sample size and clinical metadata are not detailed in the abstract
- Translatability from PET NP and murine models to heterogeneous human exposures requires validation
Future Directions: Quantify corona composition across larger clinical cohorts, assess exposure–response in humans, and evaluate inhibitors of TLR4/LXRα or efferocytosis in combination with immunotherapy.
Airborne nanoplastic (NP) pollution is an emerging threat to respiratory health. Although inhaled NPs rapidly acquire a protein corona that shapes their bioactivity, the consequences of this process in cancer-susceptible lungs remain unclear. Here, we investigated whether NPs form a disease-specific pathogenic protein corona in lung adenocarcinoma that rewires immune signaling and accelerates tumor progression. Polyethylene terephthalate (PET) NPs were generated by mechanical fragmentation and extensively characterized. In tumor-bearing mice, inhaled PET NPs accelerated tumor growth relative to controls. Proteomic analysis of PET NPs incubated with bronchoalveolar lavage fluid from patients with lung adenocarcinoma identified lysozyme (LYZ) as a selectively enriched corona component associated with tumor stage and metastasis. Corona formation induced conformational remodeling of LYZ, enhanced its enzymatic activity, and prolonged its membrane retention. Mechanistically, corona-bound LYZ engaged Toll-like receptor 4 and activated a PGRN-LXRα signaling axis, thereby increasing lysosomal acidification-dependent efferocytosis, promoting M2 macrophage polarization, and reducing CD8
3. Influenza Activity and Estimated Vaccine Effectiveness During the 2025-2026 Influenza Season.
Drifted A(H3N2) subclade K dominated the 2025–2026 U.S. season; all tested strains remained antiviral susceptible. Interim vaccine effectiveness was 35% for ED/urgent care encounters and 27% for hospitalizations, with substantial national disease burden.
Impact: Provides integrated, multi-source national estimates of circulating strains, vaccine performance, and antiviral susceptibility to guide in-season clinical and public health decisions.
Clinical Implications: Clinicians should continue to vaccinate, test, and treat promptly with neuraminidase or cap-dependent endonuclease inhibitors; anticipate moderate VE against prevalent A(H3N2) subclade K.
Key Findings
- Of 55,318 public health lab positives, 87.8% of subtyped A viruses were A(H3N2); 92.7% of characterized A(H3N2) were subclade K.
- All 1,729 tested A(H3N2) viruses were susceptible to antivirals; post‑vaccination neutralizing titers vs subclade K were 1.62‑fold lower than to vaccine strain.
- Interim VE: 35% against ED/urgent care encounters and 27% against hospitalizations; estimated U.S. burden up to 49 million illnesses.
Methodological Strengths
- Multi-source surveillance integrating virology, serology, hospitalization burden, and test-negative VE
- Large-scale national datasets with standardized laboratory characterization
Limitations
- Interim VE subject to residual confounding and changes later in season
- Serology reflects neutralization but not full correlates of protection
Future Directions: Update end-of-season VE, evaluate clade‑matched vaccine composition, and assess subgroup VE and effectiveness of antiviral strategies.
IMPORTANCE: Antigenically drifted influenza A(H3N2) J.2.4.1 (subclade K) viruses predominated during the 2025-2026 Northern Hemisphere influenza season. OBJECTIVE: To describe influenza activity and burden, characterize subclade K, evaluate susceptibility to influenza antivirals and postinfluenza vaccination antibodies, and estimate vaccine effectiveness. DESIGN, SETTING, AND PARTICIPANTS: This surveillance study used multiple data sources, including (1) national surveillance of influenza-positive respiratory specimens collected by approximately 300 clinical laboratories and 100 public health laboratories from October 1, 2025, through March 14, 2026, a subset of which were further characterized; (2) serologic data of people who received 2025-2026 influenza vaccines; (3) influenza admissions data from the Influenza Hospitalization Surveillance Network (ie, 10% of US population) and the associated estimates of US burden; and (4) test-negative, case-control vaccine effectiveness estimates from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network. EXPOSURES: Influenza infection, hospitalization, and vaccination. MAIN OUTCOMES AND MEASURES: Outcomes included influenza virus type, subtype, and clade; antiviral susceptibility; immunogenicity; influenza-associated outpatient and emergency department visits, hospitalizations, and mortality; estimated influenza illnesses, hospitalizations, and death; and estimated vaccine effectiveness. RESULTS: As of March 14, 2026, of the 55 318 influenza-positive respiratory specimens tested by public health laboratories, most (50 291 specimens [90.9%]) were influenza A, of which 40 779 (81.1%) were subtyped and 35 801 (87.8%) were A(H3N2). Of the 1754 characterized A(H3N2) viruses, most (1626 specimens [92.7%]) were subclade K. Postinfluenza vaccination neutralizing geometric mean antibody titers against subclade K were reduced 1.62 (95% CI, 1.29-2.02)-fold compared with the vaccine virus. All 1729 tested A(H3N2) viruses were sensitive to antivirals. Of the 27 881 recorded influenza hospitalizations, 15 426 (54.7%) were among female patients, and 15 051 (54.0%) were among patients aged 65 years or older. The estimated cumulative influenza-associated hospitalization rate was 80.0 per 100 000 which would correlate with estimates of between 28 000 000 to 49 000 000 illnesses, 360 000 to 740 000 hospitalizations, and 22 000 to 74 000 deaths in the US during the 2025-2026 season. Adjusted interim vaccine effectiveness estimates against influenza-associated emergency department or urgent care encounters and hospitalizations were 35% (95% CI, 33%-38%) and 27% (95% CI, 21%-34%), respectively. CONCLUSIONS AND RELEVANCE: This surveillance study found that while antigenically drifted viruses predominated and caused substantial morbidity and mortality, influenza vaccines were associated with a reduced risk of influenza among those who were vaccinated, and recommended antivirals remained effective.