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Original Research

A Virus-Like-Particle immunotherapy targeting Epitope-Specific anti-xCT expressed on cancer stem cell inhibits the progression of metastatic cancer in vivo

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Article: e1408746 | Received 25 Aug 2017, Accepted 18 Nov 2017, Published online: 06 Dec 2017

References

  • Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016;13:674–90. doi:10.1038/nrclinonc.2016.66.
  • Visvader JE, Stingl J. Mammary stem cells and the differentiation hierarchy: current status and perspectives. Genes & Dev. 2014;28:1143–58. doi:10.1101/gad.242511.114.
  • Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755–68. doi:10.1038/nrc2499.
  • Fulawka L, Donizy P, Halon A. Cancer stem cells–the current status of an old concept: literature review and clinical approaches. Biol Res. 2014;47:66. doi:10.1186/0717-6287-47-66. PMID:25723910.
  • Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012;21:283–96. doi:10.1016/j.ccr.2012.03.003.
  • Nagano O, Okazaki S, Saya H. Redox regulation in stem-like cancer cells by CD44 variant isoforms. Oncogene. 2013;32:5191–8. doi:10.1038/onc.2012.638.
  • Chen RS, Song YM, Zhou ZY, Tong T, Li Y, Fu M, Guo XL, Dong LJ, He X, Qiao HX, et al. Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/beta-catenin pathway. Oncogene. 2009;28:599–609. doi:10.1038/onc.2008.414.
  • Guo W, Zhao Y, Zhang Z, Tan N, Zhao F, Ge C, Liang L, Jia D, Chen T, Yao M, et al. Disruption of xCT inhibits cell growth via the ROS/autophagy pathway in hepatocellular carcinoma. Cancer Lett. 2011;312:55–61. doi:10.1016/j.canlet.2011.07.024. PMID:21906871.
  • Gasol E, Jimenez-Vidal M, Chillaron J, Zorzano A, Palacin M. Membrane topology of system xc- light subunit reveals a re-entrant loop with substrate-restricted accessibility. J Biol Chem. 2004;279:31228–36. doi:10.1074/jbc.M402428200.
  • Sato H, Tamba M, Okuno S, Sato K, Keino-Masu K, Masu M, Bannai S. Distribution of cystine/glutamate exchange transporter, system x(c)-, in the mouse brain. J Neurosci: the official journal of the Society for Neuroscience. 2002;22:8028–33.
  • Miyazaki I, Murakami S, Torigoe N, Kitamura Y, Asanuma M. Neuroprotective effects of levetiracetam target xCT in astrocytes in parkinsonian mice. J Neurochem. 2016;136:194–204. doi:10.1111/jnc.13405.
  • Lanzardo S, Conti L, Rooke R, Ruiu R, Accart N, Bolli E, Arigoni M, Macagno M, Barrera G, Pizzimenti S, et al. Immunotargeting of Antigen xCT Attenuates Stem-like Cell Behavior and Metastatic Progression in Breast Cancer. Cancer Res. 2016;76:62–72. doi:10.1158/0008-5472.CAN-15-1208.
  • Briggs KJ, Koivunen P, Cao S, Backus KM, Olenchock BA, Patel H, Zhang Q, Signoretti S, Gerfen GJ, Richardson AL, et al. Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. Cell. 2016;166:126–39. doi:10.1016/j.cell.2016.05.042.
  • Gyorffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, Szallasi Z. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat. 2010;123:725–31. doi:10.1007/s10549-009-0674-9.
  • Lu H, Samanta D, Xiang L, Zhang H, Hu H, Chen I, Bullen JW, Semenza GL. Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype. Proc Natl Acad Sci U S A. 2015;112:E4600−9. doi:10.1073/pnas.1513433112.
  • Nishino M, Ozaki M, Hegab AE, Hamamoto J, Kagawa S, Arai D, Yasuda H, Naoki K, Soejima K, Saya H, et al. Variant CD44 expression is enriching for a cell population with cancer stem cell-like characteristics in human lung adenocarcinoma. J Cancer. 2017;8:1774–85. doi:10.7150/jca.19732.
  • Polewski MD, Reveron-Thornton RF, Cherryholmes GA, Marinov GK, Aboody KS. SLC7A11 Overexpression in Glioblastoma Is Associated with Increased Cancer Stem Cell-Like Properties. Stem Cells Dev. 2017. doi:10.1089/scd.2017.0123. PMID:28610554.
  • Song Y, Jang J, Shin TH, Bae SM, Kim JS, Kim KM, Myung SJ, Choi EK, Seo HR. Sulfasalazine attenuates evading anticancer response of CD133-positive hepatocellular carcinoma cells. Journal of experimental & clinical cancer research: CR. 2017;36:38. doi:10.1186/s13046-017-0511-7.
  • Zavros Y. Initiation and Maintenance of Gastric Cancer: A Focus on CD44 Variant Isoforms and Cancer Stem Cells. Cell Mol Gastroenterol Hepatol. 2017;4:55–63. doi:10.1016/j.jcmgh.2017.03.003.
  • Ju HQ, Lu YX, Chen DL, Tian T, Mo HY, Wei XL, Liao JW, Wang F, Zeng ZL, Pelicano H, et al. Redox Regulation of Stem-like Cells Though the CD44v-xCT Axis in Colorectal Cancer: Mechanisms and Therapeutic Implications. Theranostics. 2016;6:1160–75. doi:10.7150/thno.14848.
  • Yoshikawa M, Tsuchihashi K, Ishimoto T, Yae T, Motohara T, Sugihara E, Onishi N, Masuko T, Yoshizawa K, Kawashiri S, et al. xCT inhibition depletes CD44v-expressing tumor cells that are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma. Cancer Res. 2013;73:1855–66. doi:10.1158/0008-5472.CAN-12-3609-T.
  • Hasegawa M, Takahashi H, Rajabi H, Alam M, Suzuki Y, Yin L, Tagde A, Maeda T, Hiraki M, Sukhatme VP, et al. Functional interactions of the cystine/glutamate antiporter, CD44v and MUC1-C oncoprotein in triple-negative breast cancer cells. Oncotarget. 2016;7:11756–69. doi:10.18632/oncotarget.7598.
  • Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, Ikeda T, Asaba R, Yagi H, Masuko T, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer cell. 2011;19:387–400. doi:10.1016/j.ccr.2011.01.038.
  • Pore N, Jalla S, Liu Z, Higgs B, Sorio C, Scarpa A, Hollingsworth R, Tice DA, Michelotti E. In Vivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors. Neoplasia. 2015;17:473–80. doi:10.1016/j.neo.2015.05.001.
  • Guan J, Lo M, Dockery P, Mahon S, Karp CM, Buckley AR, Lam S, Gout PW, Wang YZ. The xc- cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine. Cancer Chem Pharmacol. 2009;64:463–72. doi:10.1007/s00280-008-0894-4.
  • Timmerman LA, Holton T, Yuneva M, Louie RJ, Padro M, Daemen A, Hu M, Chan DA, Ethier SP, van 't Veer LJ, et al. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer cell. 2013;24:450–65. doi:10.1016/j.ccr.2013.08.020.
  • Robe PA, Martin DH, Nguyen-Khac MT, Artesi M, Deprez M, Albert A, Vanbelle S, Califice S, Bredel M, Bours V. Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults. BMC Cancer. 2009;9:372. doi:10.1186/1471-2407-9-372. PMID:19840379.
  • Gout PW, Buckley AR, Simms CR, Bruchovsky N. Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x(c)- cystine transporter: a new action for an old drug. Leukemia. 2001;15:1633–40.
  • Andreasson K, Tegerstedt K, Eriksson M, Curcio C, Cavallo F, Forni G, Dalianis T, Ramqvist T. Murine pneumotropic virus chimeric Her2/neu virus-like particles as prophylactic and therapeutic vaccines against Her2/neu expressing tumors. International journal of cancer Journal international du cancer. 2009;124:150–6. doi:10.1002/ijc.23920.
  • Bachmann MF, Jennings GT. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol. 2010;10:787–96. doi:10.1038/nri2868.
  • Tumban E, Muttil P, Escobar CA, Peabody J, Wafula D, Peabody DS, Chackerian B. Preclinical refinements of a broadly protective VLP-based HPV vaccine targeting the minor capsid protein, L2. Vaccine. 2015;33:3346–53. doi:10.1016/j.vaccine.2015.05.016.
  • Chackerian B, Caldeira Jdo C, Peabody J, Peabody DS. Peptide epitope identification by affinity selection on bacteriophage MS2 virus-like particles. Journal of molecular biology. 2011;409:225–37. doi:10.1016/j.jmb.2011.03.072.
  • Caldeira Jdo C, Medford A, Kines RC, Lino CA, Schiller JT, Chackerian B, Peabody DS. Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7. Vaccine. 2010;28:4384–93.
  • Peabody DS, Manifold-Wheeler B, Medford A, Jordan SK, do Carmo Caldeira J, Chackerian B. Immunogenic display of diverse peptides on virus-like particles of RNA phage MS2. J mol biol. 2008;380:252–63. doi:10.1016/j.jmb.2008.04.049.
  • Caldeira J, Bustos J, Peabody J, Chackerian B, Peabody DS. Epitope-Specific Anti-hCG Vaccines on a Virus Like Particle Platform. PloS One. 2015;10:e0141407. doi:10.1371/journal.pone.0141407. PMID:26516771.
  • Crossey E, Amar MJ, Sampson M, Peabody J, Schiller JT, Chackerian B, Remaley AT. A cholesterol-lowering VLP vaccine that targets PCSK9. Vaccine. 2015;33:5747–55. doi:10.1016/j.vaccine.2015.09.044.
  • O'Rourke JP, Daly SM, Triplett KD, Peabody D, Chackerian B, Hall PR. Development of a mimotope vaccine targeting the Staphylococcus aureus quorum sensing pathway. PloS one. 2014;9:e111198. doi:10.1371/journal.pone.0111198. PMID:25379726.
  • Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, Massie A, Smolders I, Methner A, Pergande M, et al. The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxidants & redox signaling. 2013;18:522–55. doi:10.1089/ars.2011.4391.
  • Conti L, Lanzardo S, Arigoni M, Antonazzo R, Radaelli E, Cantarella D, Calogero RA, Cavallo F. The noninflammatory role of high mobility group box 1/Toll-like receptor 2 axis in the self-renewal of mammary cancer stem cells. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2013;27:4731–44. doi:10.1096/fj.13-230201.
  • Pulaski BA, Ostrand-Rosenberg S. Mouse 4T1 breast tumor model. Current protocols in immunology / edited by John E Coligan [et al]. 2001; Chapter 20:Unit 20 2.
  • Tallerico R, Todaro M, Di Franco S, Maccalli C, Garofalo C, Sottile R, Palmieri C, Tirinato L, Pangigadde PN, La Rocca R, et al. Human NK cells selective targeting of colon cancer-initiating cells: a role for natural cytotoxicity receptors and MHC class I molecules. J Immunol. 2013;190:2381–90. doi:10.4049/jimmunol.1201542.
  • Tallerico R, Conti L, Lanzardo S, Sottile R, Garofalo C, Wagner AK, Johansson MH, Cristiani CM, Kärre K, Carbone E, et al. NK cells control breast cancer and related cancer stem cell hematological spread. Oncoimmunology. 2017;6:e1284718. doi:10.1080/2162402X.2017.1284718. PMID:28405511.
  • Lollini PL, Cavallo F, Nanni P, Forni G. Vaccines for tumour prevention. Nat Rev Cancer. 2006;6:204–16. doi:10.1038/nrc1815. PMID:16498443.
  • Cavallo F, Calogero RA, Forni G. Are oncoantigens suitable targets for anti-tumour therapy? Nat Rev Cancer. 2007;7:707–13. doi:10.1038/nrc2208.
  • Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature. 2015;523:231–5. doi:10.1038/nature14404.
  • Hong Y, Manoharan I, Suryawanshi A, Majumdar T, Angus-Hill ML, Koni PA, Manicassamy B, Mellor AL, Munn DH, Manicassamy S. beta-catenin promotes regulatory T-cell responses in tumors by inducing vitamin A metabolism in dendritic cells. Cancer Res. 2015;75:656–65. doi:10.1158/0008-5472.CAN-14-2377.
  • Sehm T, Fan Z, Ghoochani A, Rauh M, Engelhorn T, Minakaki G, Dörfler A, Klucken J, Buchfelder M, Eyüpoglu IY, et al. Sulfasalazine impacts on ferroptotic cell death and alleviates the tumor microenvironment and glioma-induced brain edema. Oncotarget. 2016;7:36021–33. doi:10.18632/oncotarget.8651.
  • Wang F, Yang Y. Suppression of the xCT-CD44v antiporter system sensitizes triple-negative breast cancer cells to doxorubicin. Breast cancer research and treatment. 2014;147:203–10. doi:10.1007/s10549-014-3068-6.
  • Ma MZ, Chen G, Wang P, Lu WH, Zhu CF, Song M, Yang J, Wen S, Xu RH, Hu Y, et al. Xc- inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism. Cancer lett. 2015;368:88–96. doi:10.1016/j.canlet.2015.07.031.
  • Emens LA. Breast Cancer Immunotherapy: Facts and Hopes. Clinical cancer research: an official journal of the American Association for Cancer Research 2017; pii: clincanres.3001.2017. doi:10.1158/1078-0432.CCR-16-3001.
  • Tissot AC, Maurer P, Nussberger J, Sabat R, Pfister T, Ignatenko S, Volk HD, Stocker H, Müller P, Jennings GT, et al. Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. Lancet. 2008;371:821–7. doi:10.1016/S0140-6736(08)60381-5.
  • Ambuhl PM, Tissot AC, Fulurija A, Maurer P, Nussberger J, Sabat R, Nief V, Schellekens C, Sladko K, Roubicek K, et al. A vaccine for hypertension based on virus-like particles: preclinical efficacy and phase I safety and immunogenicity. J Hypertens. 2007;25:63–72. doi:10.1097/HJH.0b013e32800ff5d6.
  • Maurer P, Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K, Renner WA, Müller P, Bachmann MF. A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity. Eur J Immunol. 2005;35:2031–40. doi:10.1002/eji.200526285.
  • Chackerian B, Rangel M, Hunter Z, Peabody DS. Virus and virus-like particle-based immunogens for Alzheimer's disease induce antibody responses against amyloid-beta without concomitant T cell responses. Vaccine. 2006;24:6321–31. doi:10.1016/j.vaccine.2006.05.059.
  • Spohn G, Schori C, Keller I, Sladko K, Sina C, Guler R, Schwarz K, Johansen P, Jennings GT, Bachmann MF. Preclinical efficacy and safety of an anti-IL-1beta vaccine for the treatment of type 2 diabetes. Mol Ther Methods Clin Dev. 2014;1:14048. doi:10.1038/mtm.2014.48. PMID:26015986
  • Fotiadis D, Kanai Y, Palacin M. The SLC3 and SLC7 families of amino acid transporters. Mol Aspects Med. 2013;34:139–58. doi:10.1016/j.mam.2012.10.007.
  • Bhutia YD, Babu E, Ramachandran S, Ganapathy V. Amino Acid transporters in cancer and their relevance to “glutamine addiction”: novel targets for the design of a new class of anticancer drugs. Cancer research. 2015;75:1782–8. doi:10.1158/0008-5472.CAN-14-3745.
  • Geier EG, Schlessinger A, Fan H, Gable JE, Irwin JJ, Sali A, Giacomini KM.. Structure-based ligand discovery for the Large-neutral Amino Acid Transporter 1, LAT-1. Proc Natl Acad Sci U S A. 2013;110:5480–5. doi:10.1073/pnas.1218165110.
  • Conti L, Ruiu R, Barutello G, Macagno M, Bandini S, Cavallo F, Lanzardo S. Microenvironment, oncoantigens, and antitumor vaccination: lessons learned from BALB-neuT mice. BioMed Research International. 2014;2014:534969. doi:10.1155/2014/534969. PMID:25136593.
  • O'Rourke JP, Peabody DS, Chackerian B. Affinity selection of epitope-based vaccines using a bacteriophage virus-like particle platform. Curr Opin Virol. 2015;11:76–82.
  • Porzia A, Lanzardo S, Citti A, Cavallo F, Forni G, Santoni A, Galandrini R, Paolini R.. Attenuation of PI3K/Akt-mediated tumorigenic signals through PTEN activation by DNA vaccine-induced anti-ErbB2 antibodies. J Immunol. 2010;184:4170–7. doi:10.4049/jimmunol.0903375.
  • Conti L, Lanzardo S, Ruiu R, Cadenazzi M, Cavallo F, Aime S, Geninatti Crich S. L-Ferritin targets breast cancer stem cells and delivers therapeutic and imaging agents. Oncotarget. 2016;7:66713–27. doi:10.18632/oncotarget.10920.
  • Riccardo F, Iussich S, Maniscalco L, Lorda Mayayo S, La Rosa G, Arigoni M, De Maria R, Gattino F, Lanzardo S, Lardone E, et al. CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA. Clinical cancer research: an official journal of the American Association for Cancer Research. 2014;20:3753–62. doi:10.1158/1078-0432.CCR-13-3042.
  • Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer chemotherapy and pharmacology. 1989;24:148–54. doi:10.1007/BF00300234.
  • Regis G, Icardi L, Conti L, Chiarle R, Piva R, Giovarelli M, et al. IL-6, but not IFN-gamma, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing. Leukemia. 2009;23:2102–8.
  • Macagno M, Bandini S, Stramucci L, Quaglino E, Conti L, Balmas E, Smyth MJ, Lollini PL, Musiani P, Forni G, et al. Multiple roles of perforin in hampering ERBB-2 (Her-2/neu) carcinogenesis in transgenic male mice. J Immunol. 2014;192:5434–41. doi:10.4049/jimmunol.1301248.
  • Jordan WH, Young JK, Hyten MJ, Hall DG. Preparation and analysis of the central nervous system. Toxicologic pathology. 2011;39:58–65. doi:10.1177/0192623310391480.