Immune gene signatures for predicting durable clinical benefit of anti-PD-1 immunotherapy in patients with non-small cell lung cancer.

Immune checkpoint blockade is promising for treating non-small-cell lung cancer (NSCLC). We used multipanel markers to predict the response to immune checkpoint inhibitors (ICIs) by characterizing gene expression signatures or individual genes in patients who showed durable clinical benefit to ICIs. Twenty-one patients with NSCLC treated with single-agent anti-programmed cell death protein (PD)-1 antibody were analyzed and their clinicopathological characteristics and response to ICIs were characterized. Nine (43%) showed a durable clinical benefit (DCB), while the remaining 12 (57%) patients showed non-durable benefit (NDB). The M1 and peripheral T cell signatures showed the best performance for discriminating DCB from NDB (sensitivity, specificity, accuracy = 0.89, 1.0, 0.95, respectively). Progression-free survival (PFS) was significantly longer in patients with high M1 signature or high peripheral T cell signature scores. CD137 and PSMB9 mRNA expression was higher in the DCB group than in the NDB group. Patients with high PSMB9 expression showed longer PFS. M1 signature, peripheral T cell signature and high mRNA expression level of CD137 and PSMB9 showed better predictive performance than known biomarkers, such as PD-L1 immunohistochemistry, tumor mutation burden, or tumor-infiltrating lymphocytes.

Rapid, Reliable, and Inexpensive HLA-B*58:01 Detection Method Using DNA Binding Dye-based Duplex Allele-specific Melting Curve Analysis.

BACKGROUND: Allopurinol is the most commonly used drug for the treatment of gout and also one of the most common causes of severe cutaneous adverse reactions (SCARs). Human leukocyte antigen-B*58:01 (HLA-B*58:01) is strongly associated with allopurinol-induced SCARs. The aim of the present study was to develop and validate a rapid and economic screening method for HLA-B*58:01. METHODS: The accuracy of duplex allele-specific melting curve analysis using DNA-binding dye for HLA-B*58:01 was evaluated in 150 blood samples with sequence-based typing (SBT) as the reference method. RESULTS: Fifty HLA-B*58:01-positive and 100 negative results obtained by duplex allele-specific melting curve analysis were completely in agreement with the SBT results. CONCLUSION: Duplex allele-specific melting curve analysis is a rapid, reliable and inexpensive assay that is appropriate for screening for the HLA-B*58:01 allele.

Layered double hydroxide as an efficient drug reservoir for folate derivatives.

Folic acid derivatives such as folinic acid and methotrexate (MTX) have been successfully hybridized with layered double hydroxide (LDH) by ion-exchange reaction. The X-ray diffraction patterns and spectroscopic analyses indicate that these molecules intercalated into the hydroxide interlayer space are stabilized in the tilted longitudinal monolayer mode by electrostatic interaction. No significant changes in their structural and functional properties are found in the hybrids. The cellular uptake test of MTX-LDH hybrid is carried out in the fibroblast (human tendon) and SaOS-2 cell line (Osteosarcoma, human) by in vitro MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide) assay. The initial proliferation of SaOS-2 cell is more strongly suppressed by treatment with MTX-LDH hybrid than with MTX alone. This study clearly shows that LDH not only plays a role as a biocompatible-delivery matrix for drugs but also facilitates a significant increase in the delivery efficiency.