Evaluating Antitumor Activity of Kiatomab by Targeting Cancer Stem Cell-Specific KIAA1114 Antigen in Mice

A full-length translational product of the trophinin gene, KIAA1114, is a distinctive marker of cancer stem cells in human hepatocellular carcinoma, and a mAb, Kiatomab, is specific to KIAA1114 antigen. In this study, we addressed the therapeutic potential of Kiatomab for treating both metastatic and solid tumors in mouse models. Kiatomab recognizes the linear epitope of KIAA1114, which is expressed on cell surfaces of various murine cancer cell lines. Kiatomab treatment induced potent antitumor responses in pulmonary metastasis models. Antitumor activity was mediated by the fragment crystallizable portion of Kiatomab and dependent on the host immune system. The use of Kiatomab alone as an antitumor therapy was ineffective in solid tumor models. However, in combination with cyclophosphamide, or by switching the isotype of the mAb, improved antitumor effects of Kiatomab were observed. These results suggest that Kiatomab can be used as a novel mAb for cancer immunotherapy.

Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection

Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called T(RM)-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs. First, we found that IL-7-mFc treatment augments the accumulation of pulmonary T cells in 2 ways: recruiting blood circulating T cells into the lung and expanding T cells at the lung parenchyma. Second, the blockade of T cell migration from the lymph nodes (LNs) with FTY720 treatment was not required for mounting the protective immunity to IAV with IL-7-mFc, suggesting a more important role of IL-7 in T cells in the lungs. Third, IL-7-mFc treatment also recruited various innate immune cells into the lungs. Among these cells, plasmacytoid dendritic cells (pDCs) play an important role in IL-7-mFc-mediated protective immunity through reducing the immunopathology and increasing IAV-specific cytotoxic T lymphocyte (CTL) responses. In summary, our results show that intranasal treatment with IL-7-mFc modulates pulmonary immune responses to IAV, affecting both innate and adaptive immune cells.

Erratum: Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection

In the publication by Kang et al., typographical error has been detected in acknowledgements.