A Phase I/II randomized trial of H56:IC31 vaccination and adjunctive cyclooxygenase-2-inhibitor treatment in tuberculosis patients.

Host-directed-therapy strategies are warranted to fight tuberculosis. Here we assess the safety and immunogenicity of adjunctive vaccination with the H56:IC31 candidate and cyclooxygenase-2-inhibitor treatment (etoricoxib) in pulmonary and extra-pulmonary tuberculosis patients in a randomized open-label phase I/II clinical trial (TBCOX2, NCT02503839). A total of 222 patients were screened, 51 enrolled and randomized; 13 in the etoricoxib-group, 14 in the H56:IC31-group, 12 in the etoricoxib+H56:IC31-group and 12 controls. Three Serious Adverse Events were reported in the etoricoxib-groups; two urticarial rash and one possible disease progression, no Serious Adverse Events were vaccine related. H56:IC31 induces robust expansion of antigen-specific T-cells analyzed by fluorospot and flow cytometry, and higher proportion of seroconversions. Etoricoxib reduced H56:IC31-induced T-cell responses. Here, we show the first clinical data that H56:IC31 vaccination is safe and immunogenic in tuberculosis patients, supporting further studies of H56:IC31 as a host-directed-therapy strategy. Although etoricoxib appears safe, our data do not support therapy with adjunctive cyclooxygenase-2-inhibitors.

Identification of metastasis-associated microRNAs in serum from rectal cancer patients.

MicroRNAs (miRNAs) are promising prognostic and diagnostic biomarkers due to their high stability in blood. Here we investigate the expression of miRNAs and other noncoding (nc) RNAs in serum of rectal cancer patients. Serum from 96 rectal cancer patients was profiled using small RNA sequencing and expression of small RNAs was correlated with the clinicopathological characteristics of the patients. Multiple classes of RNAs were detected, including miRNAs and fragments of tRNAs, snoRNAs, long ncRNAs, and other classes of RNAs. Several miRNAs, miRNA variants (isomiRs) and other ncRNAs were differentially expressed between Stage IV and Stage I-III rectal cancer patients, including several members of the miR-320 family. Furthermore, we show that high expression of miR-320d as well as one tRNA fragment is associated with poor survival. We also show that several miRNAs and isomiRs are differentially expressed between patients receiving preoperative chemoradiotherapy and patients who did not receive any treatment before serum collection. In summary, our study shows that the expression of miRNAs and other small ncRNAs in serum may be used to predict distant metastasis and survival in rectal cancer.