Immunotherapy最新文献

Aim: To assess a patient empowerment program (PEP) for children/adolescents with primary immunodeficiency (PID) on IgG replacement therapy regarding quality of life (QoL) in patients and proxy.Patients & methods: Health-related QoL was assessed using KIDSCREEN-27 and DISABKIDS-37 before and 6 months after PID-PEP kids in 19 children/adolescents and their parents.Results: The following three dimensions of the KIDSCREEN-27 significantly increased in children/adolescents after PID-PEP kids as compared with baseline: Psychological Well-Being, Parents & Autonomy and School Environment. Total DISABKIDS-37 index, as well as 5 of the 6 DISABKIDS-37 dimensions, significantly increased, in other words, Independence, Emotion, Social Inclusion, Social Exclusion and Physical. Evaluation of proxy instruments showed comparable results.Conclusion: PID-PEP kids significantly improved QoL in patients with PID.

Microsatellite instability (MSI) is an important biomarker in cancer. While routine methods can detect MSI in certain tumor types, in other tumor types the results may be incorrect due to differences in the MSI loci pattern. Here, we report the case of a patient with pancreatic adenocarcinoma, with confirmed MSI by two independent next-generation sequencing tests, but not by routine methods, who had progression on pembrolizumab. Comparison of the patient's MSI loci patterns with MSI+ colorectal adenocarcinoma samples showed a lower fraction of unstable loci, low resolution of a second peak in the repeat length spectrum of unstable short tandem repeats in the patient's sample, and a lower length of indels (3.7 vs 4.5 base pairs, p < 0.01).

Aim: Cryptococcus gattii causes a severe fungal infection with high mortality rate among immunosuppressed and immunocompetent individuals. Due to limitation of current antifungal treatment, new immunotherapeutic approaches are explored.Methods: This study investigated an immunization strategy utilizing heat-inactivated C. gattii with ArtinM as an adjuvant. C57BL/6 mice were intranasally immunized with heat-killed C. gattii and ArtinM was administrated either before immunization or along with HK-C. gattii. Mice were infected with C. gattii and the efficacy of the immunization protocol was evaluated.Results: Mice that received ArtinM exhibited increased levels of IL-10 and relative expression of IL-23 in the lungs, reduced fungal burden and preserved tissue integrity post-infection.Conclusion: Adjuvant ArtinM improved immunization against C. gattii infection in C57BL/6 mice.

Aim: To compare the protein-protein interactions of antibodies targeting PD-1 and its ligand (PD-L1) with their targets in an attempt to explain the antibodies' binding affinity. Materials & methods: The structural features of complexes between pembrolizumab, nivolumab, durvalumab, atezolizumab, avelumab and PD-1/PD-L1 are described, with the use of software and based on crystallographic data. Results: Pembrolizumab has more structural features, including the number and type of the bonds and total binding surface area, which could rationalize its different clinical behavior compared with nivolumab. Similarly, protein-protein interactions with PD-L1 differ among durvalumab, atezolizumab and avelumab. Conclusion: Differential protein-protein interactions between antibodies and PD-1/PD-L1 may indicate differential clinical activity; however, further research is needed to provide evidence.

Aim: To assess the long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in European routine clinical practice.Materials & methods: This prospective, noninterventional, open-label, post-authorization safety study (EUPAS5812) sourced data on adverse events, immunogenicity, treatment regimens and product administration for 106 adult patients prescribed fSCIG 10% across 17 sites in six European countries from July 2014 to February 2020.Results: In total, 1171 treatment-emergent adverse events were reported in 94 patients (88.7%); 25.5% of these events were considered related to fSCIG 10%. Positive binding antibody titers developed in three patients; no neutralizing antibodies to recombinant human hyaluronidase were detected.Conclusion: This real-world study of fSCIG 10% is the longest to date and confirms its long-term safety and tolerability in adults with antibody deficiency diseases.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, rare, life-threatening hematopoietic stem cell disorder that causes stem cell-derived cells to be vulnerable to complement-mediated lysis and manifests as hemolytic anemia, thrombosis, and peripheral blood cytopenias. C5 inhibitors, eculizumab, and ravulizumab, are recognized as the current standard of care for PNH treatment in countries where they are available. Crovalimab (PiaSky®), which is approved for the treatment of PNH, is a novel anti-C5 inhibitor with an every-4-weeks, low-volume, subcutaneous maintenance dosing regimen with the possibility for self-administration. Data from three phase III studies highlight the overall favorable benefit-risk profile of crovalimab, showing that crovalimab has promising potential to address the unmet medical and socioeconomic challenges in the PNH treatment landscape.

Aims: This paper was to scrutinize the toxicity mechanism of anti-programmed death 1 (anti-PD-1) therapy-caused spinal cord injury (SCI).Methods: Bone marrow transplant Rag1^-/- mice were used to establish SCI model.Results: Anti-PD-1 results in SCI via CD8⁺ T-cells activation, while excessive activation of CD8⁺ T-cells further aggravated SCI. Both anti-PD-1 and the activation of CD8⁺ T-cells induced the expression of apoptosis-related perforin, GrB and FasL, but suppressed PI-9 level. The opposite results were observed in the effects of neuroserpin on these factors. CD8⁺ T-cells activation induced neurotoxicity via upregulation perforin, GrB and FasL and inhibiting PI-9. Additionally, neuroserpin suppressed CD8⁺ T-cells activation via perforin/GrB/PI-9/FasL pathways.Conclusion: These results may provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1.

Background: Tumor-promoting inflammation and inflammatory cytokines are linked to immune checkpoint blockade (ICB) resistance.Methods: We assessed the associations between pre-treatment Interleukin-6 (IL-6), Interleukin-8 (IL-8) levels and on-treatment changes in IL-6, IL-8 and C-reactive protein (CRP) with ICB trial end points.Results: 27 studies representing 6,719 patients were included. Low pre-treatment IL-6 levels were associated with improved objective response rate (ORR) (odds ratio (OR) = 0.31 [0.18-0.55]) and better progression-free survival (PFS) (hazard ratio (HR) = 0.59 [0.48-0.72]) and overall survival (OS) [95% confidence interval (CI)] (HR = 0.42 [0.35-0.50]). Low pre-treatment IL-8 levels were associated with improved ORR (OR = 0.47 [0.36-0.61]) and better PFS (HR = 0.65 [0.58-0.74]) and OS (HR = 0.44 [0.39-0.51]). On-treatment decline in CRP was associated with improved ORR (OR = 0.18 [0.11-0.20]), PFS (HR = 0.40 [0.31-0.91]) and OS (HR = 0.48 [0.40-0.58]).Conclusion: Peripheral blood cytokines warrant further evaluation as enrichment and pharmacodynamic biomarkers for strategies targeting tumor-promoting inflammation.

Aim: To investigate how the sequence of checkpoint immunotherapy (CPI) and transarterial embolization (TAE) affects overall survival (OS) of patients with metastatic melanoma.Materials & methods: This retrospective cohort study included 65 patients with metastatic melanoma who underwent both TAE and CPI between September 2011 and January 2022.Results: Significantly higher OS was seen in patients who received CPI before and after embolization (22 months, 95% CI 14-NR, p < 0.001) compared with only before embolization (4.5 months 95% CI, 14-NR). ≤3 hepatic metastasis (p < 0.01), more TAE procedures (p < 0.001) and CPI sequence (before and after embolization) (p < 0.001) were independent predictors of survival.Conclusion: Metastatic melanoma patients who underwent TAE have longer survival when CPI was sequenced both before and after embolization.