The HER2 peptide nelipepimut-S (E75) vaccine (NeuVax™) in breast cancer patients at risk for recurrence: Correlation of immunologic data with clinical response

Immunotherapy

Volumn 6, Issue 5, 2014, Pages 519-531

  Schneble, Erika J ^a   Berry, John S ^a   Trappey, Francois A ^a   Clifton, Guy T ^a   Ponniah, Sathibalan ^b   Mittendorf, Elizabeth ^c   Peoples, George E ^a  

^a SAN ANTONIO MILITARY MEDICAL CENTER   (United States)

^b UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES   (United States)

^c UNIVERSITY OF TEXAS   (United States)

Author keywords

Breast cancer; E75; HER2 peptide vaccine; Immunotherapy; Nelipepimut S

Indexed keywords

GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; NELIPEPIMUT S; CANCER VACCINE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERBB2 PROTEIN, HUMAN; PEPTIDE;

ARTICLE; BREAST CANCER; CANCER IMMUNOTHERAPY; CANCER PATIENT; CANCER PREVENTION; CANCER RECURRENCE; CORRELATION ANALYSIS; HUMAN; IMMUNE RESPONSE; PRIORITY JOURNAL; RECURRENCE RISK; TREATMENT RESPONSE; BREAST NEOPLASMS; CLINICAL TRIAL (TOPIC); FEMALE; IMMUNOLOGY; IMMUNOTHERAPY; PROCEDURES;

BREAST NEOPLASMS; CANCER VACCINES; CLINICAL TRIALS AS TOPIC; FEMALE; HUMANS; IMMUNOTHERAPY; PEPTIDES; RECEPTOR, ERBB-2;

EID: 84902079425     PISSN: 1750743X     EISSN: 17507448     Source Type: Journal    
DOI: 10.2217/imt.14.22     Document Type: Article

References (70)

1. Disis ML, Smith JW, Murphy AE, Chen W, Cheever MA. In vitro generation of human cytolytic T-cells specific for peptides derived from the HER-2/neu protooncogene protein. Cancer Res. 54(4), 1071-1076 (1994).
2. Ioannides CG, Fisk B, Fan D, Biddison WE, Wharton JT, O'Brian CA. Cytotoxic T cells isolated from ovarian malignant ascites recognize a peptide derived from the HER-2/neu protooncogene. Cell. Immunol. 151(1), 225-234 (1993).
3. Baselga J, Cortes J, Kim SB et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N. Engl. J. Med. 366(2), 109-119 (2012).
4. Gianni L, Pienkowski T, Im YH et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, Phase II trial. Lancet Oncol. 13(1), 25-32 (2012).
5. Verma S, Miles D, Gianni L et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 367(19), 1783-1791 (2012).
6. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 353(16), 1659-1672 (2005).
7. Romond EH, Perez EA, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J.Med. 353(16), 1673-1684 (2005).
8. Perez EA, Romond EH, Suman VJ et al. Four-year followup of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: Joint analysis of data from NCCTG N9831 and NSABP B-31. J. Clin. Oncol. 29(25), 3366-3373 (2011).
9. Vreeland T, Trappey AF, Berry JS et al. Breast cancer patients with HER2 low-expression: An under-recognized group at significant risk for recurrence (abstract). Presented at: San Antonio Breast Cancer Symposium. San Antonio, TX, USA, 3-6 December 2013.
10. Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244(4905), 707-712 (1989).
11. Serrano-Olvera A, Duenas-Gonzalez A, Gallardo-Rincon D, Candelaria M, De La Garza-Salazar J. Prognostic, predictive and therapeutic implications of HER2 in invasive epithelial ovarian cancer. Cancer Treat. Rev. 32(3), 180-190 (2006).
12. Peoples GE, Goedegebuure PS, Andrews JV, Schoof DD, Eberlein TJ. HLA-A2 presents shared tumor-Associated antigens derived from endogenous proteins in ovarian cancer. J. Immunol. 151(10), 5481-5491 (1993).
13. Fisk B, Blevins TL, Wharton JT, Ioannides CG. Identification of an immunodominant peptide of HER-2/ neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J. Exp. Med. 181(6), 2109-2117 (1995).
14. Peoples GE, Goedegebuure PS, Smith R, Linehan DC, Yoshino I, Eberlein TJ. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neuderived peptide. Proc. Natl Acad. Sci. USA 92(2), 432-436 (1995).
15. Mittendorf EA, Holmes JP, Ponniah S, Peoples GE. The E75 HER2/neu peptide vaccine. Cancer Immunol. Immunother. 57(10), 1511-1521 (2008).
16. Disis ML, Bernhard H, Shiota FM et al. Granulocytemacrophage colony-stimulating factor: An effective adjuvant for protein and peptide-based vaccines. Blood 88(1), 202-210 (1996).
17. Armitage JO. Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor. Blood 92(12), 4491-4508 (1998).
18. Patil R, Clifton GT, Holmes JP et al. Clinical and immunologic responses of HLA-A3+ breast cancer patients vaccinated with the HER2/neu-derived peptide vaccine, E75, in a Phase I/II clinical trial. J. Am. Coll. Surg. 210(2), 140-147 (2010).
19. Sotiropoulou PA, Perez SA, Iliopoulou EG et al. Cytotoxic T-cell precursor frequencies to HER-2 (369-377) in patients with HER-2/neu-positive epithelial tumours. Br. J. Cancer 89(6), 1055-1061 (2003).
20. Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W. Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 96(9), 3102-3108 (2000).
21. Disis ML, Gooley TA, Rinn K et al. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J. Clin. Oncol. 20(11), 2624-2632 (2002).
22. Disis ML, Grabstein KH, Sleath PR, Cheever MA. Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide-based vaccine. Clin. Cancer Res. 5(6), 1289-1297 (1999).
23. Knutson KL, Schiffman K, Cheever MA, Disis ML. Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptidespecific immunity. Clin. Cancer Res. 8(5), 1014-1018 (2002).
24. Kono K, Takahashi A, Sugai H et al. Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer. Clin. Cancer Res. 8(11), 3394-3400 (2002).
25. Murray JL, Gillogly ME, Przepiorka D et al. Toxicity, immunogenicity, and induction of E75-specific tumorlytic CTLs by HER-2 peptide E75 (369-377) combined with granulocyte macrophage colony-stimulating factor in HLA-A2+ patients with metastatic breast and ovarian cancer. Clin. Cancer Res. 8(11), 3407-3418 (2002).
26. Zaks TZ, Rosenberg SA. Immunization with a peptide epitope (p369-377) from HER-2/neu leads to peptide-specific cytotoxic T lymphocytes that fail to recognize HER-2/neu+ tumors. Cancer Res. 58(21), 4902-4908 (1998).
27. Fisk B, Chesak B, Pollack MS, Wharton JT, Ioannides CG. Oligopeptide induction of a cytotoxic T lymphocyte response to HER-2/neu proto-oncogene in vitro. Cell. Immunol. 157(2), 415-427 (1994).
28. Lustgarten J, Theobald M, Labadie C et al. Identification of Her-2/Neu CTL epitopes using double transgenic mice expressing HLA-A2.1 and human CD.8. Hum. Immunol. 52(2), 109-118 (1997).
29. Disis ML, Shiota FM, Cheever MA. Human HER-2/neu protein immunization circumvents tolerance to rat neu: A vaccine strategy for 'self' tumour antigens. Immunology 93(2), 192-199 (1998).
30. Anderson BW, Peoples GE, Murray JL, Gillogly MA, Gershenson DM, Ioannides CG. Peptide priming of cytolytic activity to HER-2 epitope 369-377 in healthy individuals. Clin. Cancer Res. 6(11), 4192-4200 (2000).
31. Peoples GE, Gurney JM, Hueman MT et al. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. J. Clin. Oncol. 23(30), 7536-7545 (2005).
32. Brossart P, Zobywalski A, Grunebach F et al. Tumor necrosis factor alpha and CD40 ligand antagonize the inhibitory effects of interleukin 10 on T-cell stimulatory capacity of dendritic cells. Cancer Res. 60(16), 4485-4492 (2000).
33. Mittendorf EA, Clifton GT, Holmes JP et al. Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer 118(10), 2594-2602 (2012).
34. Peoples GE, Holmes JP, Hueman MT et al. Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin. Cancer Res. 14(3), 797-803 (2008).
35. Trappey ABJ, Vreeland T, Clifton G et al. HLA-A2 Is not a prognostic indicator in breast cancer: Implications for cancer vaccine trials (abstract). Presented at: San Antonio Breast Cancer Symposium. San Antonio, TX, USA, 3-6 December 2013.
36. Benavides LC, Gates JD, Carmichael MG et al. The impact of HER2/neu expression level on response to the E75 vaccine: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin. Cancer Res. 15(8), 2895-2904 (2009).
37. Holmes JP, Clifton GT, Patil R et al. Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer 117(3), 463-471 (2011).
38. Vreeland TJ, Clifton GT, Hale DF et al. Final results of the Phase I/II trials of the E75 adjuvant breast cancer vaccine. Cancer Res. 72(24 Suppl.), P5-16-02 (2012).
39. Walker EB, Disis ML. Monitoring immune responses in cancer patients receiving tumor vaccines. Int. Rev. Immunol. 22(3-4), 283-319 (2003).
40. Miles D, Roche H, Martin M et al. Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist 16(8), 1092-1100 (2011).
41. Kroemer G, Zitvogel L, Galluzzi L. Victories and deceptions in tumor immunology: Stimuvax. Oncoimmunology 2(1), e23687 (2013).
42. Cancervax. CancerVax announces results of Phase 3 clinical trials of Canvaxin™ in patients with stage III and stage IV melanoma. www.sec.gov/Archives/edgar/containers/fix060/1131907/000 093639206000264/ a18983e425.htm
43. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: Moving beyond current vaccines. Nat. Med. 10(9), 909-915 (2004).
44. Hailemichael Y, Dai Z, Jaffarzad N et al. Persistent antigen at vaccination sites induces tumor-specific CD8(+) T cell sequestration, dysfunction and deletion. Nat. Med. 19(4), 465-472 (2013).
45. Woll MM, Fisher CM, Ryan GB et al. Direct measurement of peptide-specific CD8+ T cells using HLA-A2:Ig dimer for monitoring the in vivo immune response to a HER2/ neu vaccine in breast and prostate cancer patients. J. Clin. Immunol. 24(4), 449-461 (2004).
46. Salcedo R, Resau JH, Halverson D et al. Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells. FASEB J. 14(13), 2055-2064 (2000).
47. Dehqanzada ZA, Storrer CE, Hueman MT et al. Assessing serum cytokine profiles in breast cancer patients receiving a HER2/neu vaccine using Luminex technology. Oncol. Rep. 17(3), 687-694 (2007).
48. Neumark E, Sagi-Assif O, Shalmon B, Ben-Baruch A, Witz IP. Progression of mouse mammary tumors: MCP-1-TNFalpha cross-regulatory pathway and clonal expression of promalignancy and antimalignancy factors. Int. J. Cancer 106(6), 879-886 (2003).
49. Saji H, Koike M, Yamori T et al. Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer 92(5), 1085-1091 (2001).
50. Salcedo R, Ponce ML, Young HA et al. Human endothelial cells express CCR2 and respond to MCP-1: Direct role of MCP-1 in angiogenesis and tumor progression. Blood 96(1), 34-40 (2000).
51. Dehqanzada ZA, Storrer CE, Hueman MT et al. Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients. Clin. Cancer Res. 12(2), 478-486 (2006).
52. Gershon RK, Kondo K. Cell interactions in the induction of tolerance: The role of thymic lymphocytes. Immunology 18(5), 723-737 (1970).
53. Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: A common basis between tumor immunity and autoimmunity. J. Immunol. 163(10), 5211-5218 (1999).
54. Coutinho A, Hori S, Carvalho T, Caramalho I, Demengeot J. Regulatory T cells: The physiology of autoreactivity in dominant tolerance and 'quality control' of immune responses. Immunol. Rev. 182, 89-98 (2001).
55. Hueman MT, Stojadinovic A, Storrer CE et al. Analysis of naive and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine. Cancer Immunol. Immunother. 56(2), 135-146 (2007).
56. Mittendorf EA, Gurney JM, Storrer CE, Shriver CD, Ponniah S, Peoples GE. Vaccination with a HER2/neu peptide induces intra-And inter-Antigenic epitope spreading in patients with early stage breast cancer. Surgery 139(3), 407-418 (2006).
57. Stojadinovic A, Moskovitz O, Gallimidi Z et al. Prospective study of electrical impedance scanning for identifying young women at risk for breast cancer. Breast Cancer Res. Treat. 97(2), 179-189 (2006).
58. Riethdorf S, Fritsche H, Muller V et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: A validation study of the CellSearch system. Clin. Cancer Res. 13(3), 920-928 (2007).
59. Cristofanilli M, Budd GT, Ellis MJ et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351(8), 781-791 (2004).
60. Cristofanilli M, Hayes DF, Budd GT et al. Circulating tumor cells: A novel prognostic factor for newly diagnosed metastatic breast cancer. J. Clin. Oncol. 23(7), 1420-1430 (2005).
61. Hayes DF, Cristofanilli M, Budd GT et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin. Cancer Res. 12(14 Pt 1), 4218-4224 (2006).
62. Stojadinovic A, Mittendorf EA, Holmes JP et al. Quantification and phenotypic characterization of circulating tumor cells for monitoring response to a preventive HER2/neu vaccine-based immunotherapy for breast cancer: A pilot study. Ann. Surg. Oncol. 14(12), 3359-3368 (2007).
63. Gates J, Stojadinovic A, Benavides L. Abstract 2833: Assessment of circulating tumor cells (CTCs) for monitoring immediate and long-Term response to primary and booster innoculations with a preventative HER2/neu vaccine in breast cancer patients. Presented at: American Association Cancer Research 2008 Annual Meeting. San Diego, CA, USA, 12-16 April 2008.
64. Bidard FC, Mathiot C, Delaloge S et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann. Oncol. 21(4), 729-733 (2010).
65. Rack BK, Schindlbeck C, Andergassen U et al. Use of circulating tumor cells (CTC) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy to predict risk for relapse: The SUCCESS trial. J. Clin. Oncol. 28(15 Suppl.), 1003 (2010).
66. Berry JS, Trappey AF, Vreeland TJ et al. Biomarker correlation to clinical response in Phase I/II Trials of the Adjuvant Breast Cancer Vaccine, NeuVax (nelipepimut-S or E75) (abstract). Presented at: American Society of Clinical Oncologists Annual Meeting. Chicago, IL, USA, 31 May-4 June 2013.
67. Berry J, Trappey A, Aden J et al. Predicting Clinical Benefit after Completion of Treatment with the Adjuvant Breast Cancer (BCa) Vaccine, NeuVax (nelipepimut-S or E75) (abstract). Presented at: American College of Surgeons 99th Annual Congress. Washington, DC, USA. 6-10 October 2013.
68. Efficacy and safety study of NeuVax(TM)(nelipepimut-S or E75) vaccine to prevent breast cancer recurrence. http://clinicaltrials.gov/show/NCT01479244
69. Mittendorf EA, Storrer CE, Shriver CD, Ponniah S, Peoples GE. Investigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancer. Ann. Surg. Oncol. 13(8), 1085-1098 (2006).
70. Sears AK, Clifton GT, Patil R et al. Sequential administration of trastuzumab and a CD8 T-cell-eliciting HER2/neu peptide vaccine in patients with breast cancer compared with trastuzumab alone (abstract). Presented at: ASCO Annual Meeting. Chicago, IL, USA, 3-7 June, 2011.