Evaluating Antitumor Activity of Kiatomab by Targeting Cancer Stem Cell-Specific KIAA1114 Antigen in Mice
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
Abstract
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.
참고문헌 (29)
- Coiffier B, "CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma", N Engl J Med, 346, pp.235~242 (2002)
- Baumeister SH, "Coinhibitory pathways in immunotherapy for cancer", Annu Rev Immunol, 34, pp.539~573 (2016)
- 정근옥, "Emerging Co-signaling Networks in T Cell Immune Regulation", Immune Network, 13(5), pp.184~193 (2013), 대한면역학회
- Koyama S, "Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints", Nat Commun, 7, pp.10501~ (2016)
- Woo SR, "Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape", Cancer Res, 72, pp.917~927 (2012)
- Hirsch HA, "Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission", Cancer Res, 69, pp.7507~7511 (2009)
- Pannuti A, "Targeting Notch to target cancer stem cells", Clin Cancer Res, 16, pp.3141~3152 (2010)
- Sachlos E, "Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells", Cell, 149, pp.1284~1297 (2012)
- Mehlen P, "Metastasis: a question of life or death", Nat Rev Cancer, 6, pp.449~458 (2006)
- Beck B, "Unravelling cancer stem cell potential", Nat Rev Cancer, 13, pp.727~738 (2013)
- Malanchi I, "Interactions between cancer stem cells and their niche govern metastatic colonization", Nature, 481, pp.85~89 (2011)
- Mani SA, "The epithelial-mesenchymal transition generates cells with properties of stem cells", Cell, 133, pp.704~715 (2008)
- Reya T, "Stem cells, cancer, and cancer stem cells", Nature, 414, pp.105~111 (2001)
- Magee JA, "Cancer stem cells: impact, heterogeneity, and uncertainty", Cancer Cell, 21, pp.283~296 (2012)
- Kim SW, "KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes", Oncotarget, 5, pp.1226~1240 (2014)
- Im SJ, "Natural form of noncytolytic flexible human Fc as a long-acting carrier of agonistic ligand, erythropoietin", PLoS One, 6, pp.e24574~ (2011)
- Srinivasan P, "Epitope-based immunoinformatics and molecular docking studies of nucleocapsid protein and ovarian tumor domain of Crimean-Congo hemorrhagic fever virus", Front Genet, 2, pp.72~ (2011)
- Martin AR, "Antibody engineering", pp.33~51 (2010), Springer Berlin Heidelberg
- Palermo MS, "Cyclophosphamide augments ADCC by increasing the expression of Fc-receptors", Immunol Lett, 15, pp.83~87 (1987)
- Palermo MS, "Cyclophosphamide inhibits antibody-dependent cellular cytotoxicity (ADCC) suppression exerted by lymph node cells", Cell Immunol, 93, pp.438~446 (1985)
- Nimmerjahn F, "Divergent immunoglobulin g subclass activity through selective Fc receptor binding", Science, 310, pp.1510~1512 (2005)
- Wolterink S, "Therapeutic antibodies to human L1CAM: functional characterization and application in a mouse model for ovarian carcinoma", Cancer Res, 70, pp.2504~2515 (2010)
- Vieira P, "The half-lives of serum immunoglobulins in adult mice", Eur J Immunol, 18, pp.313~316 (1988)
- Shiraga E, "A metronomic schedule of cyclophosphamide combined with PEGylated liposomal doxorubicin has a highly antitumor effect in an experimental pulmonary metastatic mouse model", Int J Pharm, 353, pp.65~73 (2008)
- Ishida T, "Synergistic antitumor activity of metronomic dosing of cyclophosphamide in combination with doxorubicin-containing PEGylated liposomes in a murine solid tumor model", J Control Release, 134, pp.194~200 (2009)
- Harada O, "The role of trophinin, an adhesion molecule unique to human trophoblasts, in progression of colorectal cancer", Int J Cancer, 121, pp.1072~1078 (2007)
- Huang J, "HMGB1 promotes drug resistance in osteosarcoma", Cancer Res, 72, pp.230~238 (2012)
- Yang L, "Up-regulated autophagy by endogenous high mobility group box-1 promotes chemoresistance in leukemia cells", Leuk Lymphoma, 53, pp.315~322 (2012)
- Chomez P, "An overview of the MAGE gene family with the identification of all human members of the family", Cancer Res, 61, pp.5544~5551 (2001)