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EGFR nanovaccine in lung cancer treatment

  • Putu Bagus Anggaraditya ,
  • Putu Anda Tusta Adiputra ,
  • I Ketut Widiana ,


Abstract

Lung cancer is known as the most common malignancy in the world in terms of incidence and death rate. GLOBOCAN data in 2018 showed that its prevalence reaches 11.6% with mortality reaching 1.7 million annually. The prevalence of lung cancer in Indonesia is also considerably high; there were 25,332 cases in men and 9,374 cases in women with mortality reaching 308,660 people. In general lung cancer is classified as non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Although it is less common, SCLC has a worse prognosis with a 5 year survival rate of 6.4%. In addition, SCLC is also often diagnosed when it has metastasized or already reaced extensive stage (ES-SCLC). Although SCLC is classified as chemo-responsive cancer, the overall outcome of first-line and second-line therapy is still unsatisfactory with an ORR of 10-25%. One of characteristic of SCLC is genomic instability which relates to high level of mutations especially EGFR mutation that strongly correlate with therapeutic outcome. Therefore, targeting EGFR mutation is a sensible and potential field in developing SCLC therapy. EGFR-CpG-ODN nanovaccine is one of the potential therapeutic choices that exploit this mutation. EGFR CpG ODN nanovaccine could inhibit resistance to EGFR TKI, increased dendritic cell maturation, inhibit cancer cell proliferation and apoptosis, as well as enhance the anticancer immune response. Therefore, this therapeutic approach is a promising future therapy for SCLC petients that could improve patient’s survivability.

Keywords: EGFR-CpG-ODN EGFR mutation Lung Cancer nanovaccine

References

  1. IARC. Globocan 2018. 2018:876;1–2.
  2. World Health Organization. Cancer Country Profiles: Indonesia. Cancer Country Profiles. 2014:22–23.
  3. Herbst, R. S., Heymach, J. V. and Lippman, S. M. Lung Cancer. New England Journal of Medicine. 2008;359(13):1367–1380.
  4. Wang, S. et al. Survival changes in patients with small cell lung cancer and disparities between different sexes , socioeconomic statuses and ages. Scientific Reports. Springer US, (April). 2017:1–14.
  5. Antonia, S. J. et al. Cancer Therapy : Clinical Combination of p53 Cancer Vaccine with Chemotherapy in Patients with Extensive Stage Small Cell Lung Cancer’, Cancer Therapy: Clinical. 2006;12(3):878–888.
  6. Chiappori, A. A. et al. INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect’, Expert Opinion on Therapeutic Patents.2011;10(6):983–991.
  7. Gazdar, A. F., Bunn, P. A. and Minna, J. D. Small-cell lung cancer : what we know , what we need to know and the path forward. Nature Publishing Group. Nature Publishing Group, 2017;17(12):725–737.
  8. Satouchi M, Kotani Y, Shibata T, Ando M, Nakagawa K. Phase III Study Comparing Amrubicin Plus Cisplatin With Irinotecan Plus Cisplatin in the Treatment of Extensive-Disease Small-Cell Lung Cancer : JCOG 0509. J Clin Oncol. 2014;32(12).
  9. Lu YC, Robbins FR. Cancer immunotherapy targeting neoantigens. Seminars in Immunology. 2016:22-27.
  10. Akira S., Takeda K. Toll Like Receptor Signaling. Nat Rev Immunol. 2004; 4 : 499–511.
  11. Scherließ R, Buske S, Young K, Weber B, Rades T, Hook S. In vivo evaluation of chitosan as an adjuvant in subcutaneous vaccine formulations. Vaccine. 2013;31(42):4812-9.
  12. Aldarouish M, Wang C. Trends and advances in tumor immunology and lung cancer immunotherapy. J Exp Clin Cancer Res. 2016;1–13.
  13. Mortellaro A, Ricciardi-Castagnoli P. From vaccine practice to vaccine science: the contribution of human immunology to the prevention of infectious disease. Immunol Cell Biol. 2011; 89:332–339.
  14. Carbone D, Gandara D, Antonia S, Zielinski C, Paz-Ares L. Non–Small-Cell Lung Cancer: Role of the Immune System and Potential for Immunotherapy. Journal of Thoracic Oncology. 2015;10(7):974-984.
  15. Martinez-Lostao L, Anel A, Pardo J. How do cytotoxic lymphocytes kill cancer cells? Clin Cancer Res. 2015;21(22):5047–56.
  16. Lin C, Lin C, Lee K, Wu S, Feng P, Chen K et al. Escape from IFN-γ-dependent immunosurveillance in tumorigenesis. Journal of Biomedical Science. 2017;24(1).
  17. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011; 331:1565–1570.
  18. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011; 480:480–489.
  19. Terme M, Pernot S, Pointet A. Immunomodulatory Activity of VEGF in Cancer. 1st ed. International Review of Cell and Molecular Biology. Elsevier Inc.2016:295-342.
  20. Liu T, Jin X, Wang Y, Wang K. Role of epidermal growth factor receptor in lung cancer and targeted therapies. 2017;7(2):187–202.
  21. Lemmon MA and Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010; 141: 1117-1134.
  22. Krause DS and Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005; 353: 172-187.
  23. Marmor MD, Skaria KB and Yarden Y. Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys 2004; 58: 903-913.
  24. Li X, Min M, Du N, Gu Y, Hode T, Naylor M et al. Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine. Clinical and Developmental Immunology. 2013;2013:1-8.
  25. Zhao Y, Zhang S, Wang P, Fu S, Wu D, Liu A. Seleno-short-chain chitosan induces apoptosis in human non-small-cell lung cancer A549 cells through ROS-mediated mitochondrial pathway. Cytotechnology. 2017;69(6):851-63.
  26. Y. Zhao, R. D. Park, and R. A. A. Muzzarelli, “Chitin deacetylases: properties and applications,†Marine Drugs, vol. 8, no. 1, pp. 24–46, 2010.
  27. S. Song, F. Zhou, R. E. Nordquist, R. Carubelli, H. Liu, and W. R. Chen, “Glycated chitosan as a new non-toxic immunological stimulant Glycated chitosan immunological stimulant,†Immunopharmacology and Immunotoxicology, vol. 31, no. 2, pp. 202–208, 2009.
  28. F. Xu, H. Liu, X. Wu et al., “Measurement of x-ray attenuation coefficients of aqueous solutions of indocyanine green and glycated chitosan,†Medical Physics, vol. 26, no. 7, pp. 1371–1374, 1999
  29. Zhou, S. Song, W. R. Chen et al., “Immunostimulatory properties of glycated chitosan,†Journal of X-Ray Science and Technology, vol. 19, no. 2, pp. 285–292, 2011.
  30. R. C. Read, S. C. Naylor, C. W. Potter et al., “Effective nasal influenza vaccine delivery using chitosan,†Vaccine, vol. 23, no. 35, pp. 4367–4374, 2005.
  31. E. A. McNeela, I. Jabbal-Gill, L. Illum et al., “Intranasal immunization with genetically detoxified diphtheria toxin induces T cell responses in humans: enhancement of Th2 responses and toxin-neutralizing antibodies by formulation with chitosan,†Vaccine, vol. 22, no. 8, pp. 909–914, 2004
  32. Zaharoff, D.A.; Rogers, C.J.; Hance, K.W.; Schlom, J. and Greiner, J.W. Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination. Vaccine. 2007, 25(11),2085–2094.
  33. Asadi GM, Rasaee MJ, RajabiBazl M, Khosravani M, Motaghinejad M, Javanmardi M, et al. A novel recombinant anti-epidermal growth factor receptor peptide vaccine capable of active immunization and reduction of tumor volume in a mouse model. Microbiol Immunol. 2017;61(12):531-38.
  34. Danay S and Tania C. CIMAvax-EGF: A New Therapeutic Vaccine for Advanced Non-Small Cell Lung Cancer Patients. Front Immunol. 2017;8:269.
  35. Codony SJ, Garcia RS, Molina VM, Bertran A J, Glimenez CA, Viteri S, et al. Anti-Epidermal Growth Factor Vaccine Antibodies Enhance the Efficacy of Tyrosine Kinase Inhibitors and Delay the Emergence of Resistance in EGFR Mutant Lung Cancer Cells. J Thorac Oncol. 2018;13(9):1324-37.
  36. Yuan S, Qiato T, Zhuang X, Chen W, Chen X, Zhang Q. Toll-like receptor 9 activation by CpG oligodeoxynucleotide 7909 enhances the radiosensitivity of A549 lung cancer cells via the p53 signaling pathway. Oncol Lett. 2018;15(4):5271-5279.
  37. Akira S., Takeda K. Toll Like Receptor Signaling. Nat Rev Immunol. 2004; 4 : 499–511.
  38. Shirota H., Klinman DM. Recent progress concerning CpG DNA and its use as a vaccine adjuvant. Expert Rev Vaccine. 2014;13:299–312.
  39. Krieg AM. Therapeutic potential of Toll-Like receptor 9 activation. Nat Rev Drug Discov. 2006;5(5):471-84.
  40. Klinman DM, Klaschik S., Sato T., Tross D. CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases. Adv Drug Deliv Rev. 2009; 61:248–55.
  41. Gursel M, Gursel I. Development of CpG ODN Based Vaccine Adjuvant Formulations. Methods Mol Biol. 2016;1404:289-98.
  42. Christian B, Gan Z, Folkert S, Takeshi K and Dennis MK. CPG DNA as a vaccine adjuvant. Expert Rev Vaccines. 2011;10(4):499-511.
  43. Ebben JD, Lubet RA, Gad E, Disis ML, You M. Epidermal Growth Factor Receptor Derived Peptide Vaccination to Prevent Lung Adenocarcinoma Formation : An In Vivo Study in a Murine Model of EGFR Mutant Lung Cancer. Mol Carcinog. 2016;55(11):1517-1525.
  44. Song S, Zhou F, Nordquist RE, Carubelli R, Liu H, Chen WR. Glycated chitosan as a new non-toxic immunological stimulant. 2009;31(November 2008):202–8.
  45. Pitaksuteepong, T. Nanoparticles : A Vaccine Adjuvant for Subcutaneous Administration. Naresuan University Journal. 2005;13(2):53-62
  46. Kuai, R. et al. Subcutaneous Nanodisc Vaccination with Neoantigens for Combination Cancer Immunotherapy. Bioconjug Chem. 2018;29(3): 771–775.
  47. Soong RS, Trieu J, Lee SY, He L, Tsai YC, Wu Tc, et al. Xenogeneic Human p53 DNA Vaccination by Electroporation Breaks Immune Tolerance to Control Murine Tumors Expressing Mouse p53. PLoS ONE. 2013;8(2):4–11.
  48. Oussoren, C. and Storm, G. Liposomes to target the lymphatics by subcutaneous administration. 2001; 50:143–156.
  49. Melief CJ, Van Hall T, Arens R, Ossendorp F, Van der Burg SH. Therapeutic cancer vaccines. J Clin Invest. 2015;125(9):3401-12.
  50. Bode, C., Zhao, G. and Steinhagen, F. CpG DNA as a vaccine adjuvant. Expert Review. 2011:499–511.
  51. Gartner, Leslie P, and James L. Hiatt. Color Textbook of Histology. Philadelphia, PA: Saunders/Elsevier, 2007.
  52. Noll BO, McCluskie MJ, Sniatala T, Lohner A, Yuill S, Krieg AM, et al. Biodistribution and metabolism of immunostimulatory oligodeoxynucleotide CPG 7909 in mouse and rat tissues following subcutaneous administration. Biochem Pharmacol. 2005;69:981–991.
  53. Sen M, Joyce S, Panahandeh M, et al: Targeting Stat3 abrogates EGFR inhibitor resistance in cancer. Clin Cancer Res. 2012;18:4986-96.
  54. Codony-Servat C, Codony-Servat J, Karachaliou N, et al: Activation of signal transducer and activator of transcription 3 (STAT3) signaling in EGFR mutant non-small-cell lung cancer (NSCLC). Oncotarget. 2017;8:47305-16.
  55. Du YC, Lin P, Zhang J, Lu YR, Ning QZ, Wang Q. Fusion of CpG-ODN-stimulating dendritic cells with Lewis lung cancer cells can enhance anti-tumor immune responses. Tissue Antigens. 2006;67(5):368–76.
  56. Takahashi R, Sato T, Klinman DM, Shimosato T, Kaneko T, Ishigatsubo Y. Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells. Int J Oncol. 2013;42(2):429-36.
  57. Chang CC, Hung CM, Yang YR, Lee MJ, Hsu YC. Sulforaphane induced cell cycle arrest in the G2/M phase via the blockade of cyclin B1/CDC2 in human ovarian cancer cells. J Ovarian Res.2013;6:41.
  58. Zhang CG, Huang JC, Liu T, Li XY. Anticancer effects of bishydroxycoumarin are mediated through apoptosis induction, cell migration inhibition and cell cycle arrest in human glioma cells. Original Artic.2015;20:1592–1600
  59. Shu G, Yang J, Zhao W, Xu C, Hong Z, Mei Z, Yang X. Kurarinol induces hepatocellular carcinoma cell apoptosis through suppressing cellular signal transducer and activator of transcription 3 signaling. Toxicol Appl Pharmacol. 2014;281:157–165.
  60. Su JY, Luo X, Zhang XJ. Immunosupressive activity of pogostone on T cells: blocking proliferation via S phase arrest. Int Immunopharmacol. 2015;26:328–337.
  61. Jiang G, Liu J, Ren B, Tang Y, Owusu L, Li M, Zhang J, Liu L, Li W. Anti-tumor effects of osthole on ovarian cancer cells in vitro. J Ethnopharmacol. 2016;193:368–376.
  62. Ma WD, Zou YP, Wang P, Yao XH, Sun Y, Duan MH, Fu YJ, Yu B. Chimaphilin induces apoptosis in human breast cancer MCF-7 cells through a ROS-mediated mitochondrial pathway. Food Chem Toxicol. 2014;70:1–8.
  63. Zaiss DMW, van Loosdregt J., Gorlani A., Bekker CPJ, Gröne A., Sibilia M., et al. Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor . Immunity.2013;38:275–284.
  64. Hardbower DM, Coburn LA, Asim M., Singh K., Sierra JC, Barry DP, et al. EGFR-mediated macrophage activation promotes colitis-associated tumorigenesis. Oncogene. 2017;36: 3807-3819.
  65. Felicity M and Dietmar MWZ. The Immune System's Contribution to the Clinical Efficacy of EGFR Antagonist Treatment. Front Pharmacol. 2017;8:575.
  66. Arab S, Motamedi M, Khansari N, Moazzeni SM, Gheflati Z, Hadjati J. Dendritic cell maturation with CpG for tumor immunotherapy. Iran J Immunol. 2006;3(3):99–105.
  67. Johnathan DE, Ronald AL, Ekram G, Mary LD, and Ming Y. Epidermal Growth Factor Receptor Derived Peptide Vaccination to Prevent Lung Adenocarcinoma Formation: An In Vivo Study in a Murine Model of EGFR Mutant Lung Cancer. Mol Carcinog. 2016;55(11):1517-25.

How to Cite

Anggaraditya, P. B., Adiputra, P. A. T., & Widiana, I. K. (2019). EGFR nanovaccine in lung cancer treatment. Bali Medical Journal, 8(3), 844–851. https://doi.org/10.15562/bmj.v8i3.1494
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Putu Bagus Anggaraditya
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Putu Anda Tusta Adiputra
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I Ketut Widiana
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