J Breast Cancer.  2018 Dec;21(4):343-353. 10.4048/jbc.2018.21.e47.

Current Approaches in Development of Immunotherapeutic Vaccines for Breast Cancer

• Allahverdiyev A
• Tari G
• Bagirova M
• Abamor ES

• KMID: 2429812
• DOI: http://doi.org/10.4048/jbc.2018.21.e47

Abstract

Cancer is the leading cause of death worldwide. In developed as well as developing countries, breast cancer is the most common cancer found among women. Currently, treatment of breast cancer consists mainly of surgery, chemotherapy, hormone therapy, and radiotherapy. In recent years, because of increased understanding of the therapeutic potential of immunotherapy in cancer prevention, cancer vaccines have gained importance. Here, we review various immunotherapeutic breast cancer vaccines including peptide-based vaccines, whole tumor cell vaccines, gene-based vaccines, and dendritic cell vaccines. We also discuss novel nanotechnology-based approaches to improving breast cancer vaccine efficiency.

Keyword

Breast neoplasms; Immunology; Immunotherapy; Vaccines

MeSH Terms

Allergy and Immunology
Breast Neoplasms*
Breast*
Cancer Vaccines
Cause of Death
Dendritic Cells
Developing Countries
Drug Therapy
Female
Humans
Immunotherapy
Radiotherapy
Vaccines*
Cancer Vaccines
Vaccines

Reference

1. American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society;2018.

2. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBACAN 2012 v1.0. Cancer ıncidence and mortality worldwide: IARC CancerBase No. 11. International Agency for Research on Cancer;Accessed May 30th, 2018. http://globocan.iarc.fr.

3. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013; 24:2206–2223. PMID: 23917950.

4. Pham PV. Breast Cancer Stem Cells & Therapy Resistance. Cham: Springer International Publishing;2015.

5. Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest. 2015; 125:3335–3337. PMID: 26325031.

6. Abbas AK, Lichman AH, Pillai S. Basic Immunology: Functions and Disorders of the Immune System. 5th ed. St. Louis: Elsevier;2015.

7. Alatrash G, Jakher H, Stafford PD, Mittendorf EA. Cancer immunotherapies, their safety and toxicity. Expert Opin Drug Saf. 2013; 12:631–645. PMID: 23668362.

8. Chung MA, Luo Y, O'Donnell M, Rodriguez C, Heber W, Sharma S, et al. Development and preclinical evaluation of a Bacillus Calmette-Guérin-MUC1-based novel breast cancer vaccine. Cancer Res. 2003; 63:1280–1287. PMID: 12649188.

9. Reichenbach DK, Finn OJ. Early in vivo signaling profiles in MUC1-specific CD4(+) T cells responding to two different MUC1-targeting vaccines in two different microenvironments. Oncoimmunology. 2013; 2:e23429. PMID: 23802084.

10. Dillon PM, Petroni GR, Smolkin ME, Brenin DR, Chianese-Bullock KA, Smith KT, et al. A pilot study of the immunogenicity of a 9-peptide breast cancer vaccine plus poly-ICLC in early stage breast cancer. J Immunother Cancer. 2017; 5:92. PMID: 29157306.

11. Mittendorf EA, Ardavanis A, Litton JK, Shumway NM, Hale DF, Murray JL, et al. Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence. Oncotarget. 2016; 7:66192–66201. PMID: 27589688.

12. Torres-García D, Pérez-Torres A, Manoutcharian K, Orbe U, Servín-Blanco R, Fragoso G, et al. GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model. Vaccine. 2017; 35:5653–5661. PMID: 28890195.

13. Gilewski T, Adluri S, Ragupathi G, Zhang S, Yao TJ, Panageas K, et al. Vaccination of high-risk breast cancer patients with mucin-1 (MUC1) keyhole limpet hemocyanin conjugate plus QS-21. Clin Cancer Res. 2000; 6:1693–1701. PMID: 10815887.

14. Vassilaros S, Tsibanis A, Tsikkinis A, Pietersz GA, McKenzie IF, Apostolopoulos V. Up to 15-year clinical follow-up of a pilot Phase III immunotherapy study in stage II breast cancer patients using oxidized mannan-MUC1. Immunotherapy. 2013; 5:1177–1182. PMID: 24188672.

15. Peoples GE, Gurney JM, Hueman MT, Woll MM, Ryan GB, Storrer CE, et al. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. J Clin Oncol. 2005; 23:7536–7545. PMID: 16157940.

16. Clifton GT, Peoples GE, Mittendorf EA. The development and use of the E75 (HER2 369-377) peptide vaccine. Future Oncol. 2016; 12:1321–1329. PMID: 27044454.

17. Hutchins LF, Makhoul I, Emanuel PD, Pennisi A, Siegel ER, Jousheghany F, et al. Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects. Oncotarget. 2017; 8:99161–99178. PMID: 29228761.

18. Borch TH, Engell-Noerregaard L, Zeeberg Iversen T, Ellebaek E, Met Ö, Hansen M, et al. mRNA-transfected dendritic cell vaccine in combination with metronomic cyclophosphamide as treatment for patients with advanced malignant melanoma. Oncoimmunology. 2016; 5:e1207842. PMID: 27757300.

19. Qi CJ, Ning YL, Han YS, Min HY, Ye H, Zhu YL, et al. Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer. Cancer Immunol Immunother. 2012; 61:1415–1424. PMID: 22290073.

20. Emens LA, Armstrong D, Biedrzycki B, Davidson N, Davis-Sproul J, Fetting J, et al. A phase I vaccine safety and chemotherapy dose-finding trial of an allogeneic GM-CSF-secreting breast cancer vaccine given in a specifically timed sequence with immunomodulatory doses of cyclophosphamide and doxorubicin. Hum Gene Ther. 2004; 15:313–337. PMID: 15018740.

21. Srivatsan S, Patel JM, Bozeman EN, Imasuen IE, He S, Daniels D, et al. Allogeneic tumor cell vaccines: the promise and limitations in clinical trials. Hum Vaccin Immunother. 2014; 10:52–63. PMID: 24064957.

22. Deacon DH, Hogan KT, Swanson EM, Chianese-Bullock KA, Denlinger CE, Czarkowski AR, et al. The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines. BMC Cancer. 2008; 8:360. PMID: 19055839.

23. Sharma A, Bode B, Wenger RH, Lehmann K, Sartori AA, Moch H, et al. Gamma-radiation promotes immunological recognition of cancer cells through increased expression of cancer-testis antigens in vitro and in vivo. PLoS One. 2011; 6:e28217. PMID: 22140550.

24. Simons JW, Sacks N. Granulocyte-macrophage colony-stimulating factor-transduced allogeneic cancer cellular immunotherapy: the GVAX vaccine for prostate cancer. Urol Oncol. 2006; 24:419–424. PMID: 16962494.

25. Huang X, Ye D, Thorpe PE. Enhancing the potency of a whole-cell breast cancer vaccine in mice with an antibody-IL-2 immunocytokine that targets exposed phosphatidylserine. Vaccine. 2011; 29:4785–4793. PMID: 21557977.

26. Convit J, Montesinos H, Oviedo H, Romero G, Maccarone B, Essenfeld E, et al. Autologous tumor lysate/Bacillus Calmette-Guérin immunotherapy as an adjuvant to conventional breast cancer therapy. Clin Transl Oncol. 2015; 17:884–887. PMID: 26077120.

27. Godoy-Calderón MJ, Salazar V, González-Marcano E, Convit AF. Autologous tumor cells/bacillus Calmette-Guérin/formalin-based novel breast cancer vaccine induces an immune antitumor response. Oncotarget. 2018; 9:20222–20238. PMID: 29755647.

28. Yan HX, Cheng P, Wei HY, Shen GB, Fu LX, Ni J, et al. Active immunotherapy for mouse breast cancer with irradiated whole-cell vaccine expressing VEGFR2. Oncol Rep. 2013; 29:1510–1516. PMID: 23404510.

29. Dols A, Smith JW 2nd, Meijer SL, Fox BA, Hu HM, Walker E, et al. Vaccination of women with metastatic breast cancer, using a costimulatory gene (CD80)-modified, HLA-A2-matched, allogeneic, breast cancer cell line: clinical and immunological results. Hum Gene Ther. 2003; 14:1117–1123. PMID: 12885350.

30. Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB, Wang XY. Therapeutic cancer vaccines: past, present, and future. Adv Cancer Res. 2013; 119:421–475. PMID: 23870514.

31. Kwilas AR, Ardiani A, Dirmeier U, Wottawah C, Schlom J, Hodge JW. A poxviral-based cancer vaccine the transcription factor twist inhibits primary tumor growth and metastases in a model of metastatic breast cancer and improves survival in a spontaneous prostate cancer model. Oncotarget. 2015; 6:28194–28210. PMID: 26317648.

32. Larocca C, Schlom J. Viral vector-based therapeutic cancer vaccines. Cancer J. 2011; 17:359–371. PMID: 21952287.

33. Bergman PJ. Cancer immunotherapy. Top Companion Anim Med. 2009; 24:130–136. PMID: 19732731.

34. Nazarkina ZhK, Khar'kova MV, Antonets DV, Morozkin ES, Bazhan SI, Karpenko LI, et al. Design of polyepitope DNA vaccine against breast carcinoma cells and analysis of its expression in dendritic cells. Bull Exp Biol Med. 2016; 160:486–490. PMID: 26915653.

35. Gelao L, Criscitiello C, Esposito A, De Laurentiis M, Fumagalli L, Locatelli MA, et al. Dendritic cell-based vaccines: clinical applications in breast cancer. Immunotherapy. 2014; 6:349–360. PMID: 24762078.

36. Peethambaram PP, Melisko ME, Rinn KJ, Alberts SR, Provost NM, Jones LA, et al. A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu. Clin Cancer Res. 2009; 15:5937–5944. PMID: 19723649.

37. Sakai Y, Morrison BJ, Burke JD, Park JM, Terabe M, Janik JE, et al. Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice. Cancer Res. 2004; 64:8022–8028. PMID: 15520211.

38. Gong J, Avigan D, Chen D, Wu Z, Koido S, Kashiwaba M, et al. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. Proc Natl Acad Sci U S A. 2000; 97:2715–2718. PMID: 10688917.

39. Koido S, Tanaka Y, Tajiri H, Gong J. Generation and functional assessment of antigen-specific T cells stimulated by fusions of dendritic cells and allogeneic breast cancer cells. Vaccine. 2007; 25:2610–2619. PMID: 17239504.

40. Bird RC, Deinnocentes P, Lenz S, Thacker EE, Curiel DT, Smith BF. An allogeneic hybrid-cell fusion vaccine against canine mammary cancer. Vet Immunol Immunopathol. 2008; 123:289–304. PMID: 18423623.

41. Bird RC, Deinnocentes P, Church Bird AE, van Ginkel FW, Lindquist J, Smith BF. An autologous dendritic cell canine mammary tumor hybrid-cell fusion vaccine. Cancer Immunol Immunother. 2011; 60:87–97. PMID: 21069323.

42. Zhang Y, Ma B, Zhou Y, Zhang M, Qiu X, Sui Y, et al. Dendritic cells fused with allogeneic breast cancer cell line induce tumor antigen-specific CTL responses against autologous breast cancer cells. Breast Cancer Res Treat. 2007; 105:277–286. PMID: 17187233.

43. Zhang Y, Luo W, Wang Y, Liu Y, Zheng L. Purified dendritic cell-tumor fusion hybrids supplemented with non-adherent dendritic cells fraction are superior activators of antitumor immunity. PLoS One. 2014; 9:e86772. PMID: 24466232.

44. Zhang P, Yi S, Li X, Liu R, Jiang H, Huang Z, et al. Preparation of triple-negative breast cancer vaccine through electrofusion with day-3 dendritic cells. PLoS One. 2014; 9:e102197. PMID: 25036145.

45. Koido S, Homma S, Hara E, Mitsunaga M, Namiki Y, Takahara A, et al. In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells. J Transl Med. 2008; 6:51. PMID: 18793383.

46. Neidhardt-Berard EM, Berard F, Banchereau J, Palucka AK. Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes. Breast Cancer Res. 2004; 6:R322–R328. PMID: 15217499.

47. Saito H, Dubsky P, Dantin C, Finn OJ, Banchereau J, Palucka AK. Cross-priming of cyclin B1, MUC-1 and survivin-specific CD8+ T cells by dendritic cells loaded with killed allogeneic breast cancer cells. Breast Cancer Res. 2006; 8:R65. PMID: 17129372.

48. Delirezh N, Moazzeni SM, Shokri F, Shokrgozar MA, Atri M, Kokhaei P. Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro. Cell Immunol. 2009; 257:23–31. PMID: 19306994.

49. Herr W, Ranieri E, Olson W, Zarour H, Gesualdo L, Storkus WJ. Mature dendritic cells pulsed with freeze-thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4(+) and CD8(+) T lymphocyte responses. Blood. 2000; 96:1857–1864. PMID: 10961887.

50. Gao Y, Chen X, Gao W, Yang Y, Ma H, Ren X. A new purification method for enhancing the immunogenicity of heat shock protein 70-peptide complexes. Oncol Rep. 2012; 28:1977–1983. PMID: 23007635.

51. Delirezh N, Moazzeni SM, Shokri F, Shokrgozar MA, Atri M, Karbassian H. In vitro analysis of T cell responses induced by breast tumor cell lysate pulsed with autologous dendritic cells. Adv Biosci Biotechnol. 2012; 3:126–136.

52. Nguyen ST, Nguyen HL, Pham VQ, Nguyen GT, Tran CD, Phan NK, et al. Targeting specificity of dendritic cells on breast cancer stem cells: in vitro and in vivo evaluations. Onco Targets Ther. 2015; 8:323–334. PMID: 25674007.

53. Kakwere H, Ingham ES, Allen R, Mahakian LM, Tam SM, Zhang H, et al. Toward personalized peptide-based cancer nanovaccines: a facile and versatile synthetic approach. Bioconjug Chem. 2017; 28:2756–2771. PMID: 28956907.

54. Razazan A, Behravan J, Arab A, Barati N, Arabi L, Gholizadeh Z, et al. Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model. PLoS One. 2017; 12:e0185099. PMID: 29045460.

55. Arab A, Behravan J, Razazan A, Gholizadeh Z, Nikpoor AR, Barati N, et al. A nano-liposome vaccine carrying E75, a HER-2/neu-derived peptide, exhibits significant antitumour activity in mice. J Drug Target. 2018; 26:365–372. PMID: 28972792.

56. Barati N, Nikpoor AR, Razazan A, Mosaffa F, Badiee A, Arab A, et al. Nanoliposomes carrying HER2/neu-derived peptide AE36 with CpG-ODN exhibit therapeutic and prophylactic activities in a mice TUBO model of breast cancer. Immunol Lett. 2017; 190:108–117. PMID: 28736158.

57. Alipour Talesh G, Ebrahimi Z, Badiee A, Mansourian M, Attar H, Arabi L, et al. Poly (I:C)-DOTAP cationic nanoliposome containing multi-epitope HER2-derived peptide promotes vaccine-elicited anti-tumor immunity in a murine model. Immunol Lett. 2016; 176:57–64. PMID: 27260485.

58. Shariat S, Badiee A, Amir Jalali S, Mansourian M, Alireza Mortazavi S, Reza Jaafari M. Preparation and characterization of different liposomal formulations containing P5 HER2/neu-derived peptide and evaluation of their immunological responses and antitumor effects. Iran J Basic Med Sci. 2015; 18:506–513. PMID: 26124938.

59. Jalali SA, Sankian M, Tavakkol-Afshari J, Jaafari MR. Induction of tumor-specific immunity by multi-epitope rat HER2/neu-derived peptides encapsulated in LPD nanoparticles. Nanomedicine. 2012; 8:692–701. PMID: 22024191.

60. Glaffig M, Palitzsch B, Hartmann S, Schüll C, Nuhn L, Gerlitzki B, et al. A fully synthetic glycopeptide antitumor vaccine based on multiple antigen presentation on a hyperbranched polymer. Chemistry. 2014; 20:4232–4236. PMID: 24623572.

61. Liu L, Wang Y, Miao L, Liu Q, Musetti S, Li J, et al. Combination immunotherapy of MUC1 mRNA nano-vaccine and CTLA-4 blockade effectively inhibits growth of triple negative breast cancer. Mol Ther. 2018; 26:45–55. PMID: 29258739.

62. Liu Z, Lv D, Liu S, Gong J, Wang D, Xiong M, et al. Alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine: effect against breast cancer in mice. PLoS One. 2013; 8:e60190. PMID: 23577091.

63. Jadidi-Niaragh F, Atyabi F, Rastegari A, Kheshtchin N, Arab S, Hassannia H, et al. CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice. J Control Release. 2017; 246:46–59. PMID: 27993599.

64. Iranpour S, Nejati V, Delirezh N, Biparva P, Shirian S. Enhanced stimulation of anti-breast cancer T cells responses by dendritic cells loaded with poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated tumor antigens. J Exp Clin Cancer Res. 2016; 35:168. PMID: 27782834.

65. Kokate RA, Chaudhary P, Sun X, Thamake SI, Maji S, Chib R, et al. Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy. Nanomedicine (Lond). 2016; 11:479–494. PMID: 26892440.

66. Campbell DF, Saenz R, Bharati IS, Seible D, Zhang L, Esener S, et al. Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles. Breast Cancer Res. 2015; 17:48. PMID: 25882711.

67. Hartmann S, Nuhn L, Palitzsch B, Glaffig M, Stergiou N, Gerlitzki B, et al. CpG-loaded multifunctional cationic nanohydrogel particles as self-adjuvanting glycopeptide antitumor vaccines. Adv Healthc Mater. 2015; 4:522–527. PMID: 25327631.

68. Roldão A, Mellado MC, Castilho LR, Carrondo MJ, Alves PM. Virus-like particles in vaccine development. Expert Rev Vaccines. 2010; 9:1149–1176. PMID: 20923267.

69. Bolli E, O'Rourke JP, Conti L, Lanzardo S, Rolih V, Christen JM, et al. A virus-like-particle immunotherapy targeting epitope-specific anti-xCT expressed on cancer stem cell inhibits the progression of metastatic cancer in vivo. Oncoimmunology. 2017; 7:e1408746. PMID: 29399412.

70. Palladini A, Thrane S, Janitzek CM, Pihl J, Clemmensen SB, de Jongh WA, et al. Virus-like particle display of HER2 induces potent anti-cancer responses. Oncoimmunology. 2018; 7:e1408749. PMID: 29399414.

71. Patel JM, Vartabedian VF, Kim MC, He S, Kang SM, Selvaraj P. Influenza virus-like particles engineered by protein transfer with tumor-associated antigens induces protective antitumor immunity. Biotechnol Bioeng. 2015; 112:1102–1110. PMID: 25689082.