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Amelioration of colorectal cancer-associated fibroblasts in immunosuppressive microenvironment by ferroptosis-based nanotherapy - PubMed
3 months ago
- Colorectal cancers (CRCs) are often resistant to immunotherapy due to cancer-associated fibroblasts (CAFs) promoting tumor growth and immunosuppression.
- A new treatment strategy uses magnetic nanoparticles to target CAFs, inducing ferroptosis (a form of cell death) through iron and copper ions.
- These nanoparticles also remodel the tumor microenvironment by breaking down physical barriers and activating the immune system, particularly dendritic cells and CD8+ T cells.
- The effectiveness of this approach is validated in patient-derived xenograft and organoid models, showing potential for clinical translation.
- The strategy offers a promising avenue for CRC treatment by addressing both structural and immunosuppressive challenges in the tumor microenvironment.
COPD reshapes the tumor microenvironment of NSCLC and enhances anti-PD-1 therapy response - PubMed
3 months ago
- COPD is a common comorbidity in NSCLC and is linked to better responses to anti-PD-1 therapy.
- COPD induces epithelial remodeling, leading to a distinct basal-like tumor cell population in NSCLC.
- These cells activate the CXCL14-CXCR4 signaling axis, recruiting macrophages that produce CXCL9.
- This creates a microenvironment that enhances cytotoxic T cell infiltration.
- The tumor-macrophage recruitment circuit is enriched in NSCLC patients with good responses to neoadjuvant anti-PD-1 therapy.
- The findings suggest a mechanistic link between COPD and improved PD-1 blockade efficacy.
- The tumor-macrophage axis could serve as a predictive biomarker and therapeutic target for immunotherapy.
Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer - PubMed
3 months ago
- Perioperative enfortumab vedotin plus pembrolizumab and surgery significantly improved event-free and overall survival in muscle-invasive bladder cancer patients ineligible for cisplatin-based chemotherapy.
- At 2 years, event-free survival was 74.7% in the treatment group vs. 39.4% in the control group (hazard ratio 0.40; P<0.001).
- Overall survival at 2 years was 79.7% in the treatment group vs. 63.1% in the control group (hazard ratio 0.50; P<0.001).
- Pathological complete response occurred in 57.1% of the treatment group vs. 8.6% in the control group (P<0.001).
- Adverse events were more common in the treatment group (grade ≥3: 71.3%) compared to the control group (grade ≥3: 45.9%).
- The study was a phase 3, open-label trial with 344 participants randomized into treatment and control groups.
Exogenous Epstein-Barr virus nuclear antigen 1 induces ADAR1-driven tumor resistance against immunotherapy - PubMed
3 months ago
- Immune checkpoint blockade (ICB) therapy faces limitations due to tumor resistance linked to suppressed interferon (IFN) signaling.
- Exogenous Epstein-Barr virus-encoded EBNA1 drives immunosuppression via enhanced ADAR1-mediated RNA editing.
- EBNA1 overexpression reduces CD8+ T-cell infiltration, inhibits IFN responses, polarizes macrophages toward M2 phenotype, and accelerates tumor growth.
- EBNA1 forms a trimeric complex with IGF2BP3 and EIF4G1, enhancing ADAR1 translation.
- Elevated ADAR1 increases A-to-I editing of dsRNA, masking immunostimulatory signals and impairing IFN pathways.
- Combining EBNA1-targeting PROTAC degrader EP-1215 with anti-PD-1 restores IFN signaling and suppresses EBNA1+ tumors in humanized mice.
- Targeting EBNA1 could convert 'cold' tumors into 'hot' targets for ICB therapy.
Adjuvant Pembrolizumab for Stage IIB or IIC Melanoma: A Secondary Analysis of a Randomized Clinical Trial - PubMed
3 months ago
- Adjuvant pembrolizumab was analyzed for its effect on new skin cancers in high-risk stage II melanoma patients.
- The study involved 976 participants, with a median follow-up of 52.8 months, comparing pembrolizumab to placebo.
- New skin cancers were less frequent in the pembrolizumab group (7.6%) compared to placebo (11.5%).
- Recurrence-free survival (RFS) benefit was maintained with pembrolizumab even after accounting for new primary melanomas.
- Immune-mediated severe skin reactions were infrequent (3.3% in pembrolizumab vs. 0.6% in placebo) and manageable.
- The findings support the use of adjuvant pembrolizumab in high-risk stage II melanoma.
Neoadjuvant therapy with an aromatase inhibitor and durvalumab in postmenopausal patients with hormone receptor-positive breast cancer - PubMed
3 months ago
- Neoadjuvant therapy combining aromatase inhibitors (AIs) and durvalumab was evaluated in postmenopausal patients with HR+/HER2-negative breast cancer.
- The study aimed to enhance the efficacy of neoadjuvant endocrine therapy by adding immunotherapy (durvalumab).
- The primary endpoint was achieving a modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0.
- 17 patients received durvalumab every 4 weeks plus daily AI for 6 months before surgery.
- Treatment was well-tolerated, with most adverse events being grade 1-2.
- 58.8% of patients showed a clinical complete response, but no pathologic complete responses occurred.
- Only 3 patients (17.6%) achieved mPEPI 0, which did not meet the criteria to proceed to the second stage of the study.
- The combination was safe but showed limited pathologic efficacy in an unselected HR+/HER2-negative population.
- Favorable long-term outcomes suggest further investigation in biomarker-selected subgroups.
Expert consensus on the detection and clinical application of tumor mutational burden - PubMed
2 months ago
- Tumor mutational burden (TMB) is an emerging biomarker for predicting tumor immunotherapy efficacy.
- TMB detection methods include whole-exome sequencing and targeted panel sequencing, but lack standardization.
- Variations in detection methods, thresholds, and reporting formats hinder TMB's clinical application.
- The consensus provides recommendations for TMB's definition, detection standardization, and clinical significance.
- Aims to help clinicians and lab personnel interpret TMB results accurately and improve patient care.
High efficiency CRISPR knock-in demonstrates that TCF1 is insufficient to reverse T cell exhaustion - PubMed
2 months ago
- CD8+ T cell exhaustion is a regulatory state caused by chronic antigen stimulation in cancer and persistent infections.
- The stem-like sub-populations of exhausted T cells are crucial for immunotherapy efficacy.
- TCF1 is necessary and sufficient for the formation and maintenance of stem-like T cell populations.
- The study investigates whether TCF1 can revert terminally exhausted T cells back to a stem-like state.
- High efficiency CRISPR knock-in was used to engineer T cells with constitutive or conditional TCF1 overexpression.
- Only constitutive TCF1 overexpression increased the stem-like T cell pool, not conditional overexpression.
- TCF1 can slow stem-like T cell differentiation but cannot revert differentiated cells back to a stem-like state.
Long-acting interleukin-7 improves the efficacy of oncolytic viral therapy in glioblastoma - PubMed
2 months ago
- Long-acting interleukin-7 (rhIL-7-hyFc) enhances oncolytic viral therapy efficacy in glioblastoma (GBM).
- The 'expand and pull' strategy increases peripheral T cell abundance and recruits them to the tumor microenvironment.
- Combining rhIL-7-hyFc with Zika virus (ZIKV) improves T cell function and delays inhibitory checkpoint receptor expression.
- Similar efficacy observed with genetically modified Δ10 3'-UTR ZIKV and oncolytic adenovirus Delta24-RGD.
- Augmenting systemic and local immune responses enhances GBM-targeted immunotherapies.
Current state of CAR-T cell therapies for solid tumors - PubMed
2 months ago
- CAR-T cell therapy has revolutionized treatment for hematological malignancies but faces challenges in solid tumors.
- Key challenges include tumor antigen heterogeneity and the immunosuppressive tumor microenvironment.
- Strategies to improve CAR-T cell efficacy in solid tumors include multi-antigen targeting and combination therapies.
- Armored CAR-T cells and synthetic engineering are among the innovative approaches being explored.
- Ongoing research is crucial to overcome existing limitations and expand CAR-T therapy to solid tumors.
Safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy from a first-in-human study of volrustomig, a novel PD-1/CTLA-4 bispecific antibody - PubMed
2 months ago
- Volrustomig is a novel PD-1/CTLA-4 bispecific antibody designed to target CTLA-4 on PD-1-positive T cells while providing durable PD-1 inhibition.
- The phase I study (NCT03530397) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy in advanced cancer patients.
- Patients received volrustomig doses ranging from 2.25-2500 mg intravenously every 3 weeks until disease progression or unacceptable toxicity.
- Common treatment-related adverse events included pruritus (30.2%), hypothyroidism (26.7%), hyperthyroidism (24.4%), and rash (24.4%).
- TRAEs led to treatment discontinuation in 33.7% of patients, with one death reported.
- At doses ≥500 mg, volrustomig showed robust peripheral and intra-tumoral T cell activation and proliferation, exceeding approved PD-1/CTLA-4 regimens.
- Objective responses were observed in 19.8% of patients, including 2.3% complete responses, with a median response duration of 17.5 months.
- Results support further development of volrustomig as monotherapy and in combination regimens, with phase 3 trials ongoing.
Clinical outcomes, serum IgG changes, and follow-up observations in the treatment of anti-AChR antibody-positive generalized myasthenia gravis with Efgartigimod - PubMed
2 months ago
- Efgartigimod treatment showed rapid clinical improvement in anti-AChR positive generalized myasthenia gravis (gMG) patients.
- 100% of patients achieved clinically meaningful reduction (CMR) in MG-ADL scores, and 87.5% in QMG scores.
- Serum IgG levels significantly decreased post-treatment, while IgA and IgM levels remained unchanged.
- Follow-up (190-414 days) showed 6 patients achieved minimal manifestation status with only grade 1 adverse events.
- One patient experienced symptom recurrence after discontinuing treatment, another had exacerbation due to respiratory infection.
- Efgartigimod, combined with immunosuppressants, helps maintain long-term disease control.
Efgartigimod for Guillain-Barré syndrome: a retrospective analysis of efficacy and safety - PubMed
2 months ago
- Efgartigimod evaluated for Guillain-Barré syndrome (GBS) in a retrospective study of 36 patients.
- Significant clinical improvement observed in both first-line and escalation therapy groups over 8 weeks.
- First-line therapy showed faster initial response and shorter time to favorable outcome (6 vs 25 days).
- Greater baseline severity and need for mechanical ventilation associated with longer recovery time.
- Exploratory analysis suggested immunomodulatory effects with decrease in certain T cell subsets.
- Only two mild adverse events reported, indicating a favorable safety profile.
- Supports further prospective evaluation of efgartigimod for GBS treatment.
Re-evaluating Treatments for Advanced Urothelial Carcinoma Using Restricted Mean Survival Time: A Systematic Review and Network Meta-analysis - PubMed
2 months ago
- The study re-evaluates treatments for advanced urothelial carcinoma (UC) using restricted mean survival time (RMST) due to potential violations of the proportional hazards (PH) assumption in immune checkpoint inhibitor (ICI) trials.
- A systematic review and network meta-analysis (NMA) of 7 phase 2/3 randomized controlled trials (2015-2025) involving 5321 patients was conducted, with individual patient data reconstructed from Kaplan-Meier curves.
- PH assumption violations were found in 50% of overall survival (OS) and 60% of progression-free survival comparisons, indicating time-dependent treatment effects not captured by traditional hazard ratios.
- ICI monotherapy showed early detriment at 12 months compared to chemotherapy (PD-1 inhibitors: -0.8 months; PD-L1 inhibitors: -0.9 months), which was masked by nonsignificant hazard ratios.
- Enfortumab vedotin + pembrolizumab demonstrated the largest RMST benefit (5.7 months at 36 months), though findings are based on a single pivotal trial and require further validation.
- The study highlights the value of RMST analysis as a complementary approach for evaluating time-dependent treatment effects in immunotherapy trials, especially where PH assumptions may not hold.
- Limitations include sparse network structure and heterogeneous patient eligibility criteria across trials.
cGAS-STING Signaling Pathway in Urogenital Oncology: Regulation, Resistance, and Routes to Response - PubMed
2 months ago
- The cGAS-STING pathway connects cytosolic DNA sensing to innate immunity and plays a critical role in urogenital cancers.
- Regulation of the pathway involves phosphorylation, ubiquitination, epigenetic repression, and metabolic reprogramming.
- Therapeutic strategies include exploiting genomic instability, reactivating STING signaling, and using engineered microbes or synthetic cyclic dinucleotides.
- Combining cGAS-STING activation with immune checkpoint blockade shows synergy but also reveals resistance mechanisms.
- Biomarkers and patient-derived models are aiding clinical translation of cGAS-STING-targeted therapies.
- Non-canonical signaling and intercellular cGAMP transport influence therapeutic responses and vulnerabilities.
Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics - PubMed
2 months ago
- Engineered 'Trikines' create three-chain cytokine receptor complexes at the cell surface.
- Trikines induce unique STAT transcriptional signaling programs distinct from natural cytokines.
- IL-2-based Trikine promotes T cell stemness and enhances tumor control without toxicity.
- IL-10-based Trikine boosts immune infiltration in poorly immunogenic tumors like small cell lung and pancreatic cancers.
- Trikines offer a cell engineering-free approach to customize STAT signatures for immunotherapy.
Lipid nanoparticle-mediated in vivo generation of panCAR immune cells for solid tumor immunotherapy - PubMed
2 months ago
- Lipid nanoparticles (LNPs) enable in vivo generation of panCAR immune cells for solid tumor immunotherapy.
- The LNP platform allows systemic delivery of CAR-encoding mRNA, engineering T cells, macrophages, dendritic cells, and NK cells across multiple tissues.
- Repeated administration of LNP-panCARHER2 inhibits tumor growth and prolongs survival in murine models without significant side effects.
- The therapy remodels the tumor microenvironment to an immunostimulatory phenotype, reducing M2-like macrophages and increasing effector T cells.
- This approach offers an off-the-shelf, in vivo CAR cell therapy platform for solid tumors.
YMN-V115: a novel humanized BCMA/GPRC5D/CD3 trispecific antibody in relapsed/refractory multiple myeloma - PubMed
2 months ago
- YMN-V115 is a novel humanized trispecific antibody targeting BCMA, GPRC5D, and CD3 for relapsed/refractory multiple myeloma (MM).
- The antibody is designed in a 1+1+1 format to enhance tumor-specific T cell engagement and reduce off-tumor toxicity.
- YMN-V115 demonstrated superior cytotoxic activity in preclinical models, outperforming bispecific antibodies.
- It maintains efficacy under soluble BCMA-saturated conditions, showing resistance to decoy inhibition.
- The trispecific antibody addresses antigenic heterogeneity by targeting both BCMA+ and GPRC5D+ tumor subsets.
- Preclinical findings support YMN-V115 as a promising next-generation therapy for MM.
Talimogene laherparepvec and atezolizumab in HER2-negative breast cancer following neoadjuvant chemotherapy: a window-of-opportunity phase II trial (SOLTI-1503 PROMETEO) - PubMed
2 months ago
- Phase II trial (SOLTI-1503 PROMETEO) investigated T-VEC (oncolytic virus) + atezolizumab (anti-PD-L1) in HER2-negative breast cancer post-neoadjuvant chemotherapy.
- 28 patients enrolled: 20 HR+/HER2-negative, 8 TNBC. 26.9% achieved RCB-0/I (primary endpoint).
- Safety profile was favorable with low-grade adverse events and no serious events (secondary endpoint).
- Therapy induced immune modulation: increased tumor-infiltrating lymphocytes, elevated PD-L1 expression, enhanced immune-related gene signatures (exploratory endpoints).
- Findings support feasibility of T-VEC + atezolizumab as preoperative immunotherapy for HER2-negative residual disease, warranting further trials.
A comparative analysis of CD70-directed CAR-T cells for glioblastoma treatment demonstrates a superior efficacy of the ligand-based construct - PubMed
2 months ago
- CD70 is a target for CAR-T cell therapy in glioblastoma (GB) due to its role in tumor growth and immunosuppression.
- Comparative analysis of CD70-directed CAR-T cells showed the ligand-based construct (CD27z) had superior efficacy.
- CD27z CAR-T cells secreted the highest levels of Th1 cytokines and demonstrated potent antitumor activity in vitro and in vivo.
- The study supports the incorporation of CD27-based CAR designs into clinical trials for recurrent GB.

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#immunotherapy

Amelioration of colorectal cancer-associated fibroblasts in immunosuppressive microenvironment by ferroptosis-based nanotherapy - PubMed

COPD reshapes the tumor microenvironment of NSCLC and enhances anti-PD-1 therapy response - PubMed

Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer - PubMed

Exogenous Epstein-Barr virus nuclear antigen 1 induces ADAR1-driven tumor resistance against immunotherapy - PubMed

Adjuvant Pembrolizumab for Stage IIB or IIC Melanoma: A Secondary Analysis of a Randomized Clinical Trial - PubMed

Neoadjuvant therapy with an aromatase inhibitor and durvalumab in postmenopausal patients with hormone receptor-positive breast cancer - PubMed

Expert consensus on the detection and clinical application of tumor mutational burden - PubMed

High efficiency CRISPR knock-in demonstrates that TCF1 is insufficient to reverse T cell exhaustion - PubMed

Long-acting interleukin-7 improves the efficacy of oncolytic viral therapy in glioblastoma - PubMed

Current state of CAR-T cell therapies for solid tumors - PubMed

Safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy from a first-in-human study of volrustomig, a novel PD-1/CTLA-4 bispecific antibody - PubMed

Clinical outcomes, serum IgG changes, and follow-up observations in the treatment of anti-AChR antibody-positive generalized myasthenia gravis with Efgartigimod - PubMed

Efgartigimod for Guillain-Barré syndrome: a retrospective analysis of efficacy and safety - PubMed

Re-evaluating Treatments for Advanced Urothelial Carcinoma Using Restricted Mean Survival Time: A Systematic Review and Network Meta-analysis - PubMed

cGAS-STING Signaling Pathway in Urogenital Oncology: Regulation, Resistance, and Routes to Response - PubMed

Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics - PubMed

Lipid nanoparticle-mediated in vivo generation of panCAR immune cells for solid tumor immunotherapy - PubMed

YMN-V115: a novel humanized BCMA/GPRC5D/CD3 trispecific antibody in relapsed/refractory multiple myeloma - PubMed

Talimogene laherparepvec and atezolizumab in HER2-negative breast cancer following neoadjuvant chemotherapy: a window-of-opportunity phase II trial (SOLTI-1503 PROMETEO) - PubMed

A comparative analysis of CD70-directed CAR-T cells for glioblastoma treatment demonstrates a superior efficacy of the ligand-based construct - PubMed