Identification of Neoantigens in Two Murine Gastric Cancer Cell Lines Leading to the Neoantigen-Based Immunotherapy.

To develop combination immunotherapies for gastric cancers, immunologically well-characterized preclinical models are crucial. Here, we leveraged two transplantable murine gastric cancer cell lines, YTN2 and YTN16, derived from the same parental line but differing in their susceptibility to immune rejection. We established their differential sensitivity to immune checkpoint inhibitors (ICI) and identified neoantigens.

Development of a novel monoclonal antibody that binds to most HLA-A allomorphs in a conformation-dependent yet peptide-promiscuous fashion.

Specificity analyses of peptide binding to human leukocyte antigen (HLA)-A molecules have been hampered due to a lack of proper monoclonal antibodies (mAbs) for certain allomorphs, such as the prevalent HLA-A1 for Caucasians and HLA-A11 for Asians. We developed a mAb that recognizes a conformational epitope common to most HLA-A allomorphs. The mAb, named A-1, does not discriminate peptides by amino acid sequences, making it suitable for measuring peptide binding.

Knockout of the interleukin-36 receptor protects against renal ischemia-reperfusion injury by reduction of proinflammatory cytokines.

IL-36, a newly named member of the IL-1 cytokine family, includes 3 isoforms, IL-36α, IL-36β, and IL-36γ, all of which bind to a heterodimer containing the IL-36 receptor (IL-36R). Little is known about the role of the IL-36 axis in acute kidney injury (AKI) pathogenesis. Therefore, we evaluated IL-36 function in the bilateral renal ischemia-reperfusion injury model of AKI using IL-36R knockout and wild-type mice.

Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes.

To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAPA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs). The peptide-loaded liposomes were taken up efficiently by DCs.

Novel combination therapy with imiquimod and sorafenib for renal cell carcinoma.

Objectives: To investigate whether the combination of the imidazoquinoline immune response modifier, imiquimod, and the multitargeted tyrosine-kinase inhibitor, sorafenib, inhibits the growth of renal cell carcinoma in mice.

Methods: Female BALB/c mice were implanted subcutaneously with 2 × 10(5) RENCA mouse kidney cancer cells, and were treated with transcutaneously applied cream containing imiquimod and oral administrations of sorafenib beginning 5 days after implantation of the cells. Tumor incidence and burden were determined at 28 days after initiation of therapy.

Centralization of dairy farming facilities for improved economics and environmental quality.

In Japan, most farm animal excreta has been stored directly on farmland. Runoff from this storage has often caused water pollution. Biogasification is anticipated as an important technology to manage excreta properly, but complex problems hinder its introduction.

Potent CTL induction by a whole cell pertussis vaccine in anti-tumor peptide immunotherapy.

Promising yet limited clinical responses have been reported for peptide based immunotherapy against tumors. In order to induce more potent cytolytic CD8 T cell responses, we investigated the use of Bordetella pertussis vaccine as an adjuvant for peptide immunization. A whole cell (Wc) vaccine has been known to induce a Th1 biased immune response while an acellular (Ac) vaccine tends to induce that of the Th2 type.