Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model

  • Authors:
    • Jan Aleksander Kraśko
    • Karolina Žilionytė
    • Adas Darinskas
    • Neringa Dobrovolskienė
    • Agata Mlynska
    • Svetlana Riabceva
    • Iosif Zalutsky
    • Marina Derevyanko
    • Vladimir Kulchitsky
    • Olga Karaman
    • Natalia Fedosova
    • Tatiana Vasyliyvna Symchych
    • Gennady Didenko
    • Vasyl Chekhun
    • Marius Strioga
    • Vita Pašukonienė
  • View Affiliations

  • Published online on: February 5, 2018     https://doi.org/10.3892/ol.2018.7950
  • Pages: 5098-5104
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Immunotherapy in the form of anticancer vaccination relies on the mobilization of the patient's immune system against specific cancer antigens. Instead of focusing on an autologous cell lysate, which is not always available in clinical practice, the present study investigates vaccines utilizing xenogeneic foetal tissue that are rich in oncofoetal antigens. Lewis lung carcinoma (LLC)‑challenged C57BL/6 mice were treated with either a xenogeneic vaccine made from chicken whole embryo, or a xenogeneic vaccine made from rat embryonic brain tissue, supplemented with a Bacillus subtilis protein fraction as an adjuvant. Median and overall survival, size of metastatic foci in lung tissue and levels of circulating CD8a+ T cells were evaluated and compared with untreated control mice. Following primary tumour removal, a course of three subcutaneous vaccinations with xenogeneic chicken embryo vaccine led to significant increase in overall survival rate (100% after 70 days of follow‑up vs. 40% in untreated control mice), significant increase in circulating CD8a+ T cells (18.18 vs. 12.6% in untreated control mice), and a significant decrease in the area and incidence of metastasis foci. The xenogeneic rat brain tissue‑based vaccine did not improve any of the investigated parameters, despite promising reports in other models. We hypothesize that the proper selection of antigen source (tissue) can constitute an effective immunotherapeutic product.

References

1 

Mittal D, Gubin MM, Schreiber RD and Smyth MJ: New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr Opin Immunol. 27:16–25. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: 2013

3 

Zitvogel L, Tesniere A and Kroemer G: Cancer despite immunosurveillance: Immunoselection and immunosubversion. Nat Rev Immunol. 6:715–727. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Galluzzi L, Vacchelli E, Bravo-San Pedro JM, et al: Classification of current anticancer immunotherapies. Oncotarget. 5:12472–12508. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G and Schadendorf D: Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 4:328–332. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Strioga M, Schijns V, Powell DJ Jr, Pasukoniene V, Dobrovolskiene N and Michalek J: Dendritic cells and their role in tumor immunosurveillance. Innate Immun. 19:98–111. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Strioga MM, Felzmann T, Powell DJ Jr, Ostapenko V, Dobrovolskiene NT, Matuskova M, Michalek J and Schijns VE: Therapeutic dendritic cell-based cancer vaccines: The state of the art. Crit Rev Immunol. 33:489–547. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Strioga MM, Darinskas A, Pasukoniene V, Mlynska A, Ostapenko V and Schijns V: Xenogeneic therapeutic cancer vaccines as breakers of immune tolerance for clinical application: To use or not to use? Vaccine. 32:4015–4024. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Weber LW, Bowne WB, Wolchok JD, Srinivasan R, Qin J, Moroi Y, Clynes R, Song P, Lewis JJ and Houghton AN: Tumor immunity and autoimmunity induced by immunization with homologous DNA. J Clin Invest. 102:1258–1264. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Overwijk WW, Lee DS, Surman DR, Irvine KR, Touloukian CE, Chan CC, Carroll MW, Moss B, Rosenberg SA and Restifo NP: Vaccination with a recombinant vaccinia virus encoding a ‘self’ antigen induces autoimmune vitiligo and tumor cell destruction in mice: requirement for CD4(+) T lymphocytes. Proc Natl Acad Sci USA. 96:pp. 2982–2987. 1999; View Article : Google Scholar : PubMed/NCBI

11 

Wei YQ, Wang QR, Zhao X, Yang L, Tian L, Lu Y, Kang B, Lu CJ, Huang MJ, Lou YY, et al: Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine. Nat Med. 6:1160–1166. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Steitz J, Brück J, Steinbrink K, Enk A, Knop J and Tüting T: Genetic immunization of mice with human tyrosinase-related protein 2: Implications for the immunotherapy of melanoma. Int J Cancer. 86:89–94. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Kornberg TB and Krasnow MA: The Drosophila genome sequence: Implications for biology and medicine. Science. 287:2218–2220. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Nilsson S, Helou K, Walentinsson A, Szpirer C, Nerman O and Ståhl F: Rat-mouse and rat-human comparative maps based on gene homology and high-resolution zoo-FISH. Genomics. 74:287–298. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Overwijk WW, Tsung A, Irvine KR, Parkhurst MR, Goletz TJ, Tsung K, Carroll MW, Liu C, Moss B, Rosenberg SA and Restifo NP: gp100/pmel 17 is a murine tumor rejection antigen: Induction of ‘self’-reactive, tumoricidal T cells using high-affinity, altered peptide ligand. J Exp Med. 188:277–286. 1998. View Article : Google Scholar : PubMed/NCBI

16 

Soong RS, Trieu J, Lee SY, He L, Tsai YC, Wu TC and Hung CF: Xenogeneic human p53 DNA vaccination by electroporation breaks immune tolerance to control murine tumors expressing mouse p53. PLoS One. 8:e569122013. View Article : Google Scholar : PubMed/NCBI

17 

Fong L, Brockstedt D, Benike C, Breen JK, Strang G, Ruegg CL and Engleman EG: Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy. J Immunol. 167:7150–7156. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Wepsic HT: Overview of oncofetal antigens in cancer. Ann Clin Lab Sci. 13:261–266. 1983.PubMed/NCBI

19 

Lim SH, Zhang Y and Zhang J: Cancer-testis antigens: The current status on antigen regulation and potential clinical use. Am J Blood Res. 2:29–35. 2012.PubMed/NCBI

20 

Malati T: Tumour markers: An overview. Indian J Clin Biochem. 22:17–31. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Ohue Y, Wada H, Oka M and Nakayama E: Antibody response to cancer/testis (CT) antigens: A prognostic marker in cancer patients. Oncoimmunology. 3:e9700322014. View Article : Google Scholar : PubMed/NCBI

22 

Symchych TV, Fedosova NI, Karaman OM, Yevstratieva LM, Lisovenko HS, Voyejkova IM and Potebnia HP: The anticancer efficiency of the xenogeneic vaccine and the indication for its use. Exp Oncol. 36:79–84. 2014.PubMed/NCBI

23 

Seledtsova GV, Shishkov AA, Kaschenko EA, Goncharov AG, Gazatova ND and Seledtsov VI: Xenogeneic cell-based vaccine therapy for stage III melanoma: Safety, immune-mediated responses and survival benefits. Eur J Dermatol. 26:138–143. 2016.PubMed/NCBI

24 

Seledtsova GV, Shishkov AA, Kaschenko EA and Seledtsov VI: Xenogeneic cell-based vaccine therapy for colorectal cancer: Safety, association of clinical effects with vaccine-induced immune responses. Biomed Pharmacother. 83:1247–1252. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Voeykova IM, Fedosova NI, Karaman OM, Yudina OY, Didenko GV, Lisovenko GS, Evstratieva LM and Potebnya GP: Use of xenogeneic vaccine modified with embryonal nervous tissue antigens in the treatment of B16-melanoma-bearing mice. Exp Oncol. 36:24–28. 2014.PubMed/NCBI

26 

Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. 33–79. 2010.

27 

Potebnya GP VI, Yudina OYu, Fedosova NI, Karaman OM, Didenko GV, Yevstratyeva LM, Lisovenko GS and Chekhun VF: The way to generate cancer vaccine. UKRPATENT: Ukraine: 2013

28 

Isokawa K, Rezaee M, Wunsch A, Markwald RR and Krug EL: Identification of transferrin as one of multiple EDTA-extractable extracellular proteins involved in early chick heart morphogenesis. J Cell Biochem. 54:207–218. 1994. View Article : Google Scholar : PubMed/NCBI

29 

Symchych TV, Fedosova NI, Karaman ОМ, Yevstratieva LM, Lisovenko HS, Voyeykova IM and Potebnia HP: Anticancer effectiveness of vaccination based on xenogeneic embryo proteins applied in different schedules. Exp Oncol. 37:197–202. 2015.PubMed/NCBI

30 

Niu PG, Zhang YX, Shi DH, Liu Y, Chen YY and Deng J: Cardamonin inhibits metastasis of lewis lung carcinoma cells by decreasing mTOR activity. PLoS One. 10:e01277782015. View Article : Google Scholar : PubMed/NCBI

31 

Schneider CA, Rasband WS and Eliceiri KW: NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 9:671–675. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Bland JM and Altman DG: The logrank test. BMJ. 328:10732004. View Article : Google Scholar : PubMed/NCBI

33 

Judge GD, William EG, Hill RC and Lee TC: The theory and practise of econometrics. John Wiley & Sons; New York: pp. 7391980

34 

Box GEP and Cox DR: An analysis of transformations. J R Stat Soc. 26:211–252. 1964.

35 

Gosset WS: The probable error of a mean. Biometrica. 6:1–25. 1908. View Article : Google Scholar

36 

Mann HB and Whitney DR: On a test of whether one of two random variables is stochastically larger than the other. Ann Math Stat. 18:50–60. 1947. View Article : Google Scholar

37 

Schirrmacher V, Fournier P and Schlag P: Autologous tumor cell vaccines for post-operative active-specific immunotherapy of colorectal carcinoma: Long-term patient survival and mechanism of function. Expert Rev Vaccines. 13:117–130. 2014. View Article : Google Scholar : PubMed/NCBI

38 

Laufer I, Iorgulescu JB, Chapman T, Lis E, Shi W, Zhang Z, Cox BW, Yamada Y and Bilsky MH: Local disease control for spinal metastases following ‘separation surgery’ and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: Outcome analysis in 186 patients. J Neurosurg Spine. 18:207–214. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Kraśko JA, Žilionytė K, Darinskas A, Strioga M, Rjabceva S, Zalutsky I, Derevyanko M, Kulchitsky V, Lubitz W, Kudela P, et al: Bacterial ghosts as adjuvants in syngeneic tumour cell lysate-based anticancer vaccination in a murine lung carcinoma model. Oncol Rep. 37:171–178. 2017. View Article : Google Scholar : PubMed/NCBI

40 

Foged C, Hansen J and Agger EM: License to kill: Formulation requirements for optimal priming of CD8(+) CTL responses with particulate vaccine delivery systems. Eur J Pharm Sci. 45:482–491. 2012. View Article : Google Scholar : PubMed/NCBI

41 

Sandoval F, Terme M, Nizard M, Badoual C, Bureau MF, Freyburger L, Clement O, Marcheteau E, Gey A, Fraisse G, et al: Mucosal imprinting of vaccine-induced CD8(+)T cells is crucial to inhibit the growth of mucosal tumors. Sci Transl Med. 5:172ra1202013. View Article : Google Scholar

42 

Chen LJ, Zheng X, Shen YP, Zhu YB, Li Q, Chen J, Xia R, Zhou SM, Wu CP, Zhang XG, et al: Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer. Cancer Immunol Immunother. 62:553–561. 2013. View Article : Google Scholar : PubMed/NCBI

43 

Noguchi A, Kaneko T, Naitoh K, Saito M, Iwai K, Maekawa R, Kamigaki T and Goto S: Impaired and imbalanced cellular immunological status assessed in advanced cancer patients and restoration of the T cell immune status by adoptive T-cell immunotherapy. Int Immunopharmacol. 18:90–97. 2014. View Article : Google Scholar : PubMed/NCBI

44 

Thiery J and Lieberman J: Perforin: A key pore-forming protein for immune control of viruses and cancer. Subcell Biochem. 80:197–220. 2014. View Article : Google Scholar : PubMed/NCBI

45 

Pérez O, Batista-Duharte A, González E, Zayas C, Balboa J, Cuello M, Cabrera O, Lastre M and Schijns VE: Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations. Braz J Med Biol Res. 45:681–692. 2012. View Article : Google Scholar : PubMed/NCBI

46 

Schijns V, Tartour E, Michalek J, Stathopoulos A, Dobrovolskiene NT and Strioga MM: Immune adjuvants as critical guides directing immunity triggered by therapeutic cancer vaccines. Cytotherapy. 16:427–439. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB and Wang XY: Therapeutic cancer vaccines: Past, present, and future. Adv Cancer Res. 119:421–475. 2013. View Article : Google Scholar : PubMed/NCBI

48 

Andersen MH, Junker N, Ellebaek E, Svane IM and Thor Straten P: Therapeutic cancer vaccines in combination with conventional therapy. J Biomed Biotechnol. 2010:2376232010. View Article : Google Scholar : PubMed/NCBI

49 

Melero I, Gaudernack G, Gerritsen W, Huber C, Parmiani G, Scholl S, Thatcher N, Wagstaff J, Zielinski C, Faulkner I and Mellstedt H: Therapeutic vaccines for cancer: An overview of clinical trials. Nat Rev Clin Oncol. 11:509–524. 2014. View Article : Google Scholar : PubMed/NCBI

50 

Cheever MA and Higano CS: PROVENGE (Sipuleucel-T) in prostate cancer: The first FDA-approved therapeutic cancer vaccine. Clin Cancer Res. 17:3520–3526. 2011. View Article : Google Scholar : PubMed/NCBI

51 

Vesely MD and Schreiber RD: Cancer immunoediting: Antigens, mechanisms, and implications to cancer immunotherapy. Ann N Y Acad Sci. 1284:1–5. 2013. View Article : Google Scholar : PubMed/NCBI

52 

Dunn GP, Old LJ and Schreiber RD: The three Es of cancer immunoediting. Annu Rev Immunol. 22:329–360. 2004. View Article : Google Scholar : PubMed/NCBI

53 

Dang Y, Wagner WM, Gad E, Rastetter L, Berger CM, Holt GE and Disis ML: Dendritic cell-activating vaccine adjuvants differ in the ability to elicit antitumor immunity due to an adjuvant-specific induction of immunosuppressive cells. Clin Cancer Res. 18:3122–3131. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

April 2018
Volume 15 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Kraśko, J.A., Žilionytė, K., Darinskas, A., Dobrovolskienė, N., Mlynska, A., Riabceva, S. ... Pašukonienė, V. (2018). Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model. Oncology Letters, 15, 5098-5104. https://doi.org/10.3892/ol.2018.7950
MLA
Kraśko, J. A., Žilionytė, K., Darinskas, A., Dobrovolskienė, N., Mlynska, A., Riabceva, S., Zalutsky, I., Derevyanko, M., Kulchitsky, V., Karaman, O., Fedosova, N., Symchych, T. V., Didenko, G., Chekhun, V., Strioga, M., Pašukonienė, V."Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model". Oncology Letters 15.4 (2018): 5098-5104.
Chicago
Kraśko, J. A., Žilionytė, K., Darinskas, A., Dobrovolskienė, N., Mlynska, A., Riabceva, S., Zalutsky, I., Derevyanko, M., Kulchitsky, V., Karaman, O., Fedosova, N., Symchych, T. V., Didenko, G., Chekhun, V., Strioga, M., Pašukonienė, V."Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model". Oncology Letters 15, no. 4 (2018): 5098-5104. https://doi.org/10.3892/ol.2018.7950