LAG-3Ig as Adjuvant for a Cancer Vaccine
Legat et al. Page 1330
Legat and colleagues report a clinical trial in 16 advanced-stage melanoma patients vaccinated with five tumor peptides, Montanide and IMP321/LAG-3Ig, a non-TLR agonist with interesting adjuvant properties including dendritic cell activation. The treatment was well tolerated. Combinatorial immune monitoring revealed multiple tumor antigen-specific CD8 and CD4 T-cell responses in most patients, supporting the further use of these vaccine components for the development of combination immunotherapies.
Surrogate Endpoints in Melanoma that Correlate with OS
Zabor et al. Page 1341
Zabor and colleagues analyzed individual patient tumor data from a phase III clinical trial of vemurafenib versus dacarbazine in melanoma patients to identify criteria for tumor measures that correlated with OS. Correlation between OS and early response was weak no matter how the response was defined; however, a strong correlation was seen between OS and progression when defined as ≥50% increase in sum of tumor diameters or appearance of new tumors. These data suggest that tumor progression is a better surrogate endpoint for OS than tumor response, such as RECIST.
Inhibition of Pancreatic Cancer by RhIL-1RA
Zhuang et al. Page 1432
Zhuang and colleagues studied whether targeting IL-1a inhibits NF-κB activity and suppresses PDAC cell growth. Previously, studies show that KRASG12V induces expression of IL-1a in genetically engineered mouse models that express mutant KRAS and p53 and in cell lines expressing KRASG12V with p16 knockdown. The authors also observed a correlation between mutant KRAS and IL-1a expression in PDAC patient samples. The experimental evidence suggests a combination of gemcitabine and IL-1 receptor antagonist can reduce PDAC cell growth by inhibiting IL-1a-induced NF-κB activity, thus suggesting a new therapeutic approach for PDAC.
CXCR4 Mutation in Waldenström Macroglobulinemia
Poulain et al. Page 1480
Poulain and colleagues analyzed the genomic landscape of CXCR4 somatic mutation in Waldenström macroglobulinemia (WM) combining deep sequencing and SNP array. The study showed existence of intraclonal (variation in coexpression of MYD88 and CXCR4 mutations) and interclonal (mutually exclusive BCR and CXCR4 mutations in MYD88L265P WM) heterogeneity of the molecular spectrum of CXCR4 mutation. Furthermore, CXCR4 mutated WM displayed a specific clinicobiologic and genomic and transcriptomic signature. This dataset further suggests the genomic heterogeneity of WM beyond the current indolent versus symptomatic classification.