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Liver metastases in advanced urothelial carcinoma (ARON-2): do pembrolizumab and avelumab make a difference in a poor-prognosis scenario? - PubMed
2 months ago
- Liver metastases in advanced urothelial carcinoma (mUC) are a poor prognostic factor.
- Two cohorts were analyzed: pembrolizumab post-platinum therapy (n=1,341) and avelumab maintenance (n=291).
- Median OS was significantly lower in patients with liver metastases (9.4 vs. 20.1 months for pembrolizumab; 16.4 vs. 27.0 months for avelumab).
- Better ECOG-PS and higher BMI (≥25 kg/m²) were associated with improved survival in both cohorts.
- Pembrolizumab and avelumab showed improved outcomes compared to historical chemotherapy data.
- The study highlights the need for personalized treatment strategies in high-risk subgroups.
Clinical development of cancer vaccines - PubMed
2 months ago
- Current immune checkpoint inhibitor therapies have limitations, necessitating improved strategies to expand tumor-reactive T cell repertoires safely and efficiently.
- Cancer vaccines show potential but have not yet matched the success of infectious disease vaccines in clinical settings.
- Recent phase 1 and 2 clinical trials have provided encouraging results, leading to large-scale cancer vaccine trials.
- Key strategies for optimizing cancer vaccines include better proxies for efficacy estimation, high-quality antigen selection (especially neoantigens), and modular vaccine platforms with innate immunostimulatory capabilities.
- Focusing on early-stage cancer, such as (neo)adjuvant therapies, is crucial for future cancer vaccine development.
- The authors disclose various advisory roles, equity holdings, and research funding from multiple biotech and pharmaceutical companies, though these relationships did not impact the study.
Bridging paradigms and shaping the future of resectable gastric cancer: a narrative review of the post-MATTERHORN era - PubMed
2 months ago
- Gastric or gastroesophageal junction cancer (GC/GEJC) is the fifth leading cause of cancer-related mortality worldwide.
- Curative-intent surgery is the cornerstone of treatment for locally advanced GC/GEJC, but recurrence remains a significant issue.
- Perioperative FLOT chemotherapy is the standard of care in Western countries, while surgery followed by adjuvant chemotherapy is standard in Asia.
- The PRODIGY and RESOLVE trials support neoadjuvant and perioperative strategies in Asia, promoting global harmonization.
- The MATTERHORN trial demonstrated significant improvements in event-free and overall survival with durvalumab added to perioperative FLOT.
- This trial provides the first global phase III evidence for integrating immune checkpoint inhibitors with perioperative chemotherapy in GC/GEJC.
- The review highlights the paradigm shift in perioperative treatment and challenges in implementing FLOT plus durvalumab in practice.
- Future directions include molecularly targeted therapies and novel multimodal approaches.
- The MATTERHORN trial marks a new era in the management of resectable GC/GEJC.
Carrier-Free Nano-Proteolysis Targeting Chimeras Enable Selective Protein Degradation and Enhance Photoimmunometabolic Therapy against Lung Adenocarcinoma - PubMed
2 months ago
- Carrier-free nanoparticles (MNC NPs) developed to enhance immunotherapy efficacy in lung adenocarcinoma.
- NPs integrate BRD4-targeting PROTAC, A2AR antagonist, and photosensitizer for synergistic therapy.
- Targets BRD4 and A2AR to alleviate immune resistance and reverse immunosuppression.
- Photosensitizer enables photodynamic therapy, promoting tumor ablation and immune activation.
- In vivo studies show suppression of primary, distant, and metastatic tumors.
- Nano-PROTACs combine protein degradation, immunometabolic reprogramming, and photodynamic immunotherapy.
Co-delivery nanoparticle targeting CAF for simultaneous activating T cell plus NKT cell attack in solid tumor - PubMed
2 months ago
- Development of FAP-α responsive nanoparticle (α-GC/NAV)-CPC targeting CAFs in solid tumors.
- Co-encapsulation of navitoclax (NAV) and alpha-galactosylceramide (α-GC) to activate NKT cells and eliminate CAFs.
- Significant reduction in tumor interstitial fluid pressure (IFP) by 4.9-fold compared to saline control.
- Increased infiltration of NKT and T cells in tumors by over 5 and 4 times respectively.
- 66.7% of mice achieved tumor eradication without recurrence in in vivo models.
- Effective prevention of lung metastatic nodules in pulmonary metastasis challenge.
Cadonilimab plus chemotherapy with or without bevacizumab as first-line treatment for advanced cervical cancer: subgroup analyses from the COMPASSION-16 phase 3 trial - PubMed
2 months ago
- Cadonilimab plus chemotherapy with or without bevacizumab shows significant progression-free survival (PFS) and overall survival (OS) benefits in advanced cervical cancer.
- Subgroup analyses from the COMPASSION-16 phase 3 trial confirm consistent improvements across diverse patient profiles.
- Key subgroups analyzed include bevacizumab use, prior chemoradiotherapy, PD-L1 CPS, metastatic disease, platinum use, and age.
- Median follow-up was 25.6 months, with hazard ratios (HRs) favoring cadonilimab in all subgroups for PFS.
- The study also reports prolonged overall survival with the addition of cadonilimab.
- Dual primary endpoints were PFS (assessed by BICR) and OS, with objective response rate as a secondary endpoint.
Benmelstobart plus anlotinib versus pembrolizumab as first-line treatment for PD-L1-positive, advanced non-small-cell lung cancer (CAMPASS): a blinded, randomised, controlled, phase 3 trial - PubMed
2 months ago
- Comparison of benmelstobart plus anlotinib versus pembrolizumab as first-line treatment for PD-L1-positive, advanced non-small-cell lung cancer (NSCLC).
- Phase 3 CAMPASS trial conducted in 79 centers across China with 531 patients enrolled.
- Primary endpoint was progression-free survival assessed by blinded independent review committee.
- Median progression-free survival was 11.0 months for benmelstobart plus anlotinib vs 7.1 months for pembrolizumab (HR 0.70, p=0.0057).
- Higher incidence of grade 3 or worse treatment-related adverse events in benmelstobart plus anlotinib group (59%) vs pembrolizumab group (29%).
- Most frequent adverse events included hypertension (26% vs 3%) and serious events like haemoptysis and immune-mediated pulmonary diseases.
- Five treatment-related deaths in benmelstobart plus anlotinib group vs four in pembrolizumab group.
- Benmelstobart plus anlotinib showed longer progression-free survival, suggesting potential as first-line treatment option.
- Longer-term follow-up needed to assess effects on overall survival.
- Funding provided by Chia Tai Tianqing Pharmaceutical Group.
Hypofractionated Radiotherapy Induces ISG15+MHC-I+ Neutrophils to Augment Anti-Tumor Immunity and Prime Immune Checkpoint Blockade Responses in Rectal Cancer - PubMed
2 months ago
- Hypofractionated radiotherapy (HFRT) combined with immunotherapy shows promise in treating locally advanced rectal cancer (LARC).
- HFRT increases ISG15+MHC-I+ neutrophil infiltration, which enhances antigen presentation and anti-tumor immunity.
- Mechanistically, HFRT promotes IFN-α release, activating the NOD1/NF-κB pathway to drive MHC-I expression in neutrophils.
- Adoptive transfer of ISG15+MHC-I+ neutrophils in mice boosts CD8+ T cell infiltration and synergizes with anti-PD-1 therapy to suppress tumor growth.
- This study identifies a novel neutrophil subset that converts 'cold' tumors to 'hot' phenotypes, improving immunotherapy efficacy in microsatellite stable LARC.
IL-7/IL-15/IL-21 cytokine-fusion scaffold generates highly functional CAR T cells enriched in long-lived T memory stem cells - PubMed
2 months ago
- HCW9206, a cytokine-fusion scaffold combining IL-7, IL-15/IL-15Rα complex, and IL-21, generates highly functional CAR T cells without requiring αCD3/28 activation.
- CAR T cells produced with HCW9206 are enriched in long-lived T memory stem cells (TSCM cells) (>50%) and show potent activity in disease models like HIV-1 and B cell leukemia.
- In a humanized mouse HIV infection model, HCW9206-generated anti-HIV duoCAR T cells suppressed viremia more effectively than αCD3/28-generated CAR T cells.
- In a xenograft leukemia mouse model, HCW9206-generated anti-CD19 CAR T cells demonstrated a recall proliferative response and complete clearance of leukemia rechallenge, unlike αCD3/28-generated CAR T cells.
- HCW9206 represents a first-in-class cytokine scaffold-based platform for producing more potent CAR T cell-based immunotherapies with enhanced persistence and functionality.
- The technology is broadly applicable for improving CAR T cell efficacy in treating infectious diseases and cancer.
Multimodal framework for the joint analysis of single-cell RNA and T cell receptor sequencing data predicts T cell response to cancer immunotherapy - PubMed
2 months ago
- TRIM is a multimodal framework integrating single-cell RNA and TCR sequencing data to predict T cell response to cancer immunotherapy.
- The model learns shared representations from patient, tissue source, and treatment timepoint data.
- Applied to datasets from head and neck squamous cell carcinoma, colorectal cancer, and a pan-cancer dataset, TRIM accurately predicted T cell clonal expansion and transcriptional status.
- The study demonstrates TRIM's utility in modeling multimodal T cell data and predicting treatment response and disease progression.
- Authors disclose various competing interests, including advisory roles and funding from biotech and pharmaceutical companies unrelated to this study.
Chimeric antigen receptor therapy for hepatocellular carcinoma - PubMed
2 months ago
- Chimeric antigen receptor (CAR) T cell therapy is being adapted from hematologic malignancies to solid tumors, including hepatocellular carcinoma (HCC).
- Solid tumors present challenges like limited immune cell infiltration, reduced T cell persistence, and antigen loss, leading to limited success in early clinical trials.
- Combinatorial strategies with next-generation armored CAR T cells and alternative immune cell types are renewing optimism in the field.
- HCC's unique liver microenvironment, influenced by lipid metabolism, bile acids, and gut-liver axis microbial compounds, presents distinct challenges and opportunities.
- HCC has various tumor-specific and tumor-associated antigens, allowing targeted approaches with minimal on-target/off-tumor effects.
- The review examines the current landscape of CAR T cell therapy for HCC, highlighting clinical and preclinical developments.
- HCC may be well-suited for tailored CAR-based strategies due to the liver's specific anatomical and immunological properties.
Complement system in cancer: friend or foe of immunotherapy - PubMed
2 months ago
- The complement system plays a dual role in cancer, influencing both tumor suppression and progression.
- Three activation pathways (classical, alternative, and lectin) initiate immune processes like opsonization and cell lysis.
- Complement activation in the tumor microenvironment can support immune-mediated tumor control or contribute to immune evasion and tumor growth.
- Therapeutic interventions like radiation and certain chemotherapies can trigger complement activation via immunogenic cell death.
- Anaphylatoxins C3a and C5a recruit immune cells but may also foster an immunosuppressive microenvironment.
- Tumor cells upregulate membrane complement regulatory proteins (CD46, CD55, CD59) to escape immune surveillance.
- Complement inhibition, particularly targeting C3aR and C5aR1, synergizes with immune checkpoint inhibitors to enhance tumor rejection.
- Combining complement blockade with proimmunogenic therapies may amplify antitumor effects.
- Strategic modulation of complement could sensitize tumors to immunotherapy and help overcome resistance mechanisms.
CT-based radiomics for predicting the treatment response to PD-1/PD-L1 inhibitors combined with chemotherapy in unresectable gastric cancer - PubMed
2 months ago
- CT-based radiomics model developed to predict immunotherapy response in unresectable gastric cancer.
- Study included 368 patients from two centers, divided into training, internal validation, and external validation cohorts.
- Radiomics signature with 15 features showed good predictive performance (AUC = 0.868 in training, 0.816 in internal validation, 0.793 in external validation).
- Logistic regression model performed best with AUC values of 0.886, 0.831, and 0.826 in respective cohorts.
- Nomogram integrating Radscore and clinical factors demonstrated satisfactory calibration and clinical utility.
- Radscore correlated with immune cell infiltration (activated CD4+ memory T cells, regulatory T cells, CD8+ T cells).
- Study provides a non-invasive, biologically-informed tool for personalized immunotherapy treatment strategies.
Neoadjuvant Immunotherapy and Chemoimmunotherapy Regimens in Head and Neck Cancer: A Systematic Review and Meta-Analysis - PubMed
2 months ago
- Neoadjuvant chemoimmunotherapy shows high pathologic response rates in head and neck squamous cell carcinoma (HNSCC).
- Meta-analysis includes 751 patients across 23 studies, comparing chemoimmunotherapy, dual-agent, and single-agent immunotherapy.
- Pooled major and complete pathologic response rates were 66% for chemoimmunotherapy, 18% for dual-agent, and 6% for single-agent immunotherapy.
- 1-year overall survival rates were high across all groups, ranging from 88% to 100%.
- Grade 3-5 adverse events were more common in chemoimmunotherapy (29%) compared to dual-agent (3%) and single-agent (17%) immunotherapy.
- Findings suggest chemoimmunotherapy is superior to immunotherapy alone, warranting phase 3 trials for direct comparison.
Real-world evidence on the efficacy, safety, and biomarkers of immunotherapy combined with radiotherapy in limited-stage small cell lung cancer - PubMed
2 months ago
- Study explores immunotherapy combined with radiotherapy in limited-stage small cell lung cancer (LS-SCLC).
- 32 patients treated with ICIs and chemotherapy, followed by radiotherapy, showed high response rates (ORR 93.7%, DCR 100%).
- Median PFS was 16.3 months and median OS was 37 months for first-line treatment.
- Key adverse events included grade 3/4 myelosuppression (15.6%) and radiation pneumonitis (18.7%).
- PLR (Platelet-to-Lymphocyte Ratio) >101.75 at baseline predicted longer PFS.
- LDH normalization during treatment suggested favorable response, though not statistically significant.
- Elevated NSE and ProGRP trends correlated with shorter PFS.
- The combination therapy is feasible, safe, and effective for LS-SCLC.
IL 15 enhances preclinical efficacy of anti-core 1 O-glycans monoclonal antibody NEO-201 against human endometrial and ovarian cancer - PubMed
2 months ago
- IL-15 enhances the efficacy of monoclonal antibody NEO-201 against endometrial and ovarian cancer.
- NEO-201 targets core 1 O-glycans on cancer cells and mediates killing via ADCC and CDC.
- Combining NEO-201 with IL-15 boosts NK cell activity, improving ADCC in vitro.
- The combination modestly prolonged survival in mice with ovarian cancer.
- Future potential includes combining NEO-201 and IL-15 with CAR-NK cell therapy.
Research progress on the compositional characteristics of the tumor immune microenvironment and immunopredictive models in esophageal squamous cell carcinoma - PubMed
2 months ago
- Esophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer.
- Immunotherapy, especially immune checkpoint inhibitors (ICIs), shows significant efficacy in advanced ESCC.
- The tumor immune microenvironment (TIME) heterogeneity affects immunotherapy outcomes and tumor behavior.
- Understanding TIME interactions and reshaping it with ICIs could offer new treatment opportunities.
- The review discusses TIME characteristics and immunopredictive models to improve ESCC immunotherapy.
Durvalumab combined with concurrent chemoradiotherapy in patients with limited-stage small cell lung cancer: A prospective, single-arm, phase 2 clinical trial - PubMed
2 months ago
- Durvalumab combined with concurrent chemoradiotherapy (cCRT) was studied in a phase 2 trial for limited-stage small cell lung cancer (LS-SCLC).
- The trial included 51 patients, with a median follow-up of 32.0 months, showing 1-, 2-, and 3-year PFS rates of 56.9%, 35.9%, and 28.2%, respectively.
- The 1-, 2-, and 3-year OS rates were 88.1%, 68.6%, and 49.6%, respectively, with a median OS of 32.0 months.
- Grade 3 or 4 adverse events occurred in 33.4% of patients, with 7 being immune-related.
- The study concluded that durvalumab with cCRT was well-tolerated and showed encouraging efficacy for LS-SCLC.
Harnessing γδ T cells for B7-H3-targeting CAR therapy to enhance anti-tumor therapy in glioblastoma - PubMed
2 months ago
- The study focuses on using γδ T cells engineered with B7-H3-targeting CAR to enhance anti-tumor therapy in glioblastoma.
- Ethics approval for human sample use was obtained from the Ethics Committee of Xuanwu Hospital, Capital Medical University, with informed consent.
- Animal experiments were approved by the Institutional Animal Care and Use Committee of Beijing Friendship Hospital, Capital Medical University.
- The authors declared no conflicts of interest and all approved the manuscript for publication.
- References include key studies on glioblastoma classification, molecular methods, immunopathology, and the tumor microenvironment.
A Silent Saboteur of Immunotherapy: Antibiotic Use and Its Impact on Immune Checkpoint Inhibitors Efficacy, a Systematic Review and Meta-Analysis of Recent Studies - PubMed
2 months ago
- Antibiotic use (ABT) negatively impacts the efficacy of immune checkpoint inhibitors (ICIs) in treating solid tumors.
- A systematic review and meta-analysis of 15 studies involving 52,489 patients found ABT exposure associated with worse overall survival (OS) and progression-free survival (PFS).
- The gut microbiota, which plays a role in antitumor immunity, is disrupted by ABT, potentially impairing ICI effectiveness.
- In non-small cell lung cancer (NSCLC), ABT exposure was consistently linked to inferior PFS and reduced OS.
- The findings highlight the need for cautious antibiotic stewardship in patients receiving ICIs and call for further research with microbiome profiling and standardized ABT exposure assessment.

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#immunotherapy

Liver metastases in advanced urothelial carcinoma (ARON-2): do pembrolizumab and avelumab make a difference in a poor-prognosis scenario? - PubMed

Clinical development of cancer vaccines - PubMed

Bridging paradigms and shaping the future of resectable gastric cancer: a narrative review of the post-MATTERHORN era - PubMed

Carrier-Free Nano-Proteolysis Targeting Chimeras Enable Selective Protein Degradation and Enhance Photoimmunometabolic Therapy against Lung Adenocarcinoma - PubMed

Co-delivery nanoparticle targeting CAF for simultaneous activating T cell plus NKT cell attack in solid tumor - PubMed

Cadonilimab plus chemotherapy with or without bevacizumab as first-line treatment for advanced cervical cancer: subgroup analyses from the COMPASSION-16 phase 3 trial - PubMed

Benmelstobart plus anlotinib versus pembrolizumab as first-line treatment for PD-L1-positive, advanced non-small-cell lung cancer (CAMPASS): a blinded, randomised, controlled, phase 3 trial - PubMed

Hypofractionated Radiotherapy Induces ISG15+MHC-I+ Neutrophils to Augment Anti-Tumor Immunity and Prime Immune Checkpoint Blockade Responses in Rectal Cancer - PubMed

IL-7/IL-15/IL-21 cytokine-fusion scaffold generates highly functional CAR T cells enriched in long-lived T memory stem cells - PubMed

Multimodal framework for the joint analysis of single-cell RNA and T cell receptor sequencing data predicts T cell response to cancer immunotherapy - PubMed

Chimeric antigen receptor therapy for hepatocellular carcinoma - PubMed

Complement system in cancer: friend or foe of immunotherapy - PubMed

CT-based radiomics for predicting the treatment response to PD-1/PD-L1 inhibitors combined with chemotherapy in unresectable gastric cancer - PubMed

Neoadjuvant Immunotherapy and Chemoimmunotherapy Regimens in Head and Neck Cancer: A Systematic Review and Meta-Analysis - PubMed

Real-world evidence on the efficacy, safety, and biomarkers of immunotherapy combined with radiotherapy in limited-stage small cell lung cancer - PubMed

IL 15 enhances preclinical efficacy of anti-core 1 O-glycans monoclonal antibody NEO-201 against human endometrial and ovarian cancer - PubMed

Research progress on the compositional characteristics of the tumor immune microenvironment and immunopredictive models in esophageal squamous cell carcinoma - PubMed

Durvalumab combined with concurrent chemoradiotherapy in patients with limited-stage small cell lung cancer: A prospective, single-arm, phase 2 clinical trial - PubMed

Harnessing γδ T cells for B7-H3-targeting CAR therapy to enhance anti-tumor therapy in glioblastoma - PubMed

A Silent Saboteur of Immunotherapy: Antibiotic Use and Its Impact on Immune Checkpoint Inhibitors Efficacy, a Systematic Review and Meta-Analysis of Recent Studies - PubMed