1.Phase II trial of combination therapy of gemcitabine plus anti-angiogenic vaccination of elpamotide in patients with advanced or recurrent biliary tract cancer.
Matsuyama M1, Ishii H, Furuse J, Ohkawa S, Maguchi H, Mizuno N, Yamaguchi T, Ioka T, Ajiki T, Ikeda M, Hakamada K, Yamamoto M, Yamaue H, Eguchi K, Ichikawa W, Miyazaki M, Ohashi Y, Sasaki Y. Invest New Drugs. 2015 Apr;33(2):490-5. doi: 10.1007/s10637-014-0197-z. Epub 2014 Dec 13.
Background Elpamotide is an HLA-A*24:02-restricted epitope peptide of vascular endothelial growth factor receptor 2 (VEGFR-2) and induces cytotoxic T lymphocytes (CTLs) against VEGFR-2/KDR. Given the high expression of VEGFR-2 in biliary tract cancer, combination chemoimmunotherapy with elpamotide and gemcitabine holds promise as a new therapy. Patients and Methods Patients with unresectable advanced or recurrent biliary tract cancer were included in this single-arm phase II trial, with the primary endpoint of overall survival. Survival analysis was performed in comparison with historical control data. The patients concurrently received gemcitabine once a week for 3 weeks (the fourth week was skipped) and elpamotide once a week for 4 weeks. Results Fifty-five patients were registered, of which 54 received the regimen and were included in the full analysis set as well as the safety analysis set. Median survival was 10.1 months, which was longer than the historical control, and the 1-year survival rate was 44.
2.Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study.
Yamaue H1, Tsunoda T1, Tani M1, Miyazawa M1, Yamao K2, Mizuno N2, Okusaka T3, Ueno H3, Boku N4, Fukutomi A4, Ishii H5, Ohkawa S6, Furukawa M7, Maguchi H8, Ikeda M9, Togashi Y10, Nishio K10, Ohashi Y11. Cancer Sci. 2015 Jul;106(7):883-90. doi: 10.1111/cas.12674. Epub 2015 May 14.
Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test was applied to the statistical analysis in this study to evaluate the time-lagged effect of immunotherapy appropriately.
3.Simian Virus 40 Infection in the Spinal Cord of Simian Immunodeficiency Virus-Immunosuppressed Rhesus Macaques.
Kaliyaperumal S1, Wüthrich C, Westmoreland SV, Koralnik IJ. J Neuropathol Exp Neurol. 2015 Nov;74(11):1071-6. doi: 10.1097/NEN.0000000000000252.
Progressive multifocal leukoencephalopathy (PML) is an often-fatal demyelinating disease of the CNS that usually develops in immunocompromised individuals because of reactivation of quiescent JC virus (JCV). There are only a few reports of JCV infection in the human spinal cord. Progressive multifocal leukoencephalopathy-like demyelinating lesions have been documented in the brains of simian immunodeficiency virus-infected macaques. To determine whether simian virus 40 (SV40) can infect and cause PML lesions in spinal cords of immunosuppressed macaques, we examined archival spinal cord samples from 15 simian immunodeficiency virus-infected rhesus monkeys with acquired immunodeficiency syndrome and SV40 infection of the brain. Among those, 6 (40%) had SV40-infected cells in the spinal cord, including 1 with PML-like lesions, 1 with PML-like lesions and meningoencephalitis, 2 with meningoencephalitis, 1 with gray matter gliosis, and 1 with no lesions.
4.Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts.
Yoon JH1, Kim J, Lee H, Kim SY, Jang HH, Ryu SH, Kim BJ, Lee TG. Biochem Biophys Res Commun. 2012 Nov 23;428(3):416-21. doi: 10.1016/j.bbrc.2012.10.070. Epub 2012 Oct 27.
The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the β1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner.
