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Original Research

A plant-expressed conjugate vaccine breaks CD4+ tolerance and induces potent immunity against metastatic Her2+ breast cancer

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Article: e1166323 | Received 02 Nov 2015, Accepted 11 Mar 2016, Published online: 09 Jun 2016

References

  • Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science 2013; 342:1432-3; PMID:24357284; http://dx.doi.org/10.1126/science.342.6165.1432
  • Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer 2012; 12:278-87; PMID:22437872; http://dx.doi.org/10.1038/nrc3236
  • Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363:711-23; PMID:20525992; http://dx.doi.org/10.1056/NEJMoa1003466
  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2011; 363:411-22; PMID:20818862; http://dx.doi.org/10.1056/NEJMoa1001294
  • ISA Pharmaceuticals. Study of a therapeutic vaccine (ISA101) to treat advanced or recurrent cervical cancer (CervISA). ClinicalTrialsgov [Internet] Bethesda (MD): NIH (US) Available from: https://clinicaltrials.gov/ct2/show/NCT02128126, Updated January 2016; cited February 2016:NLM identifier: NCT02128126.
  • CureVac AG. An open label randomised trial of RNActive® cancer vaccine in high risk and intermediate risk patients with prostate cancer. ClinicalTrialsgov [Internet] Bethesda (MD): NIH (US) Available from: https://clinicaltrials.gov/ct2/show/NCT02140138, [Updated January 2016; cited February 2016]:NLM identifier: NCT02140138.
  • CureVac AG. Trial of RNActive®-derived prostate cancer vaccine in metastatic castrate-refractory prostate cancer. ClinicalTrialsgov [Internet] Bethesda (MD): NIH (US) Available from: https://clinicaltrials.gov/ct2/show/NCT01817738, [Updated December 2013; cited February 2016]:NLM identifier: NCT01817738
  • Trimble CL, Morrow MP, Kraynyak KA, Shen X, Dallas M, Yan J, Edwards L, Parker RL, Denny L, Giffear M et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet 2015; 386:2078-88; PMID:26386540; http://dx.doi.org/10.1016/S0140-6736(15)00239-1
  • Quoix E, Lena H, Losonczy G, Forget F, Chouaid C, Papai Z, Gervais R, Ottensmeier C, Szczesna A, Kazarnowicz A et al. TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial. Lancet Oncol 2016; 17:212-23; PMID:26727163; http://dx.doi.org/10.1016/S1470-2045(15)00483-0.
  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235:177-82; PMID:3798106; http://dx.doi.org/10.1126/science.3798106
  • Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244:707-12; PMID:2470152; http://dx.doi.org/10.1126/science.2470152
  • Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, Soper JT, Dodge R, Clarke-Pearson DL, Marks P et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 1990; 50:4087-91; PMID:1972347
  • Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2:127-37; PMID:11252954; http://dx.doi.org/10.1038/35052073
  • Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med 2007; 357:39-51; PMID:17611206; http://dx.doi.org/10.1056/NEJMra043186
  • Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367:1783-91; PMID:23020162; http://dx.doi.org/10.1056/NEJMoa1209124
  • Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372:724-34; PMID:25693012; http://dx.doi.org/10.1056/NEJMoa1413513
  • Ladjemi MZ, Jacot W, Chardes T, Pelegrin A, Navarro-Teulon I. Anti-HER2 vaccines: new prospects for breast cancer therapy. Cancer Immunol Immunother 2010; 59:1295-312; PMID:20532501; http://dx.doi.org/10.1007/s00262-010-0869-2
  • Hamilton E, Blackwell K, Hobeika AC, Clay TM, Broadwater G, Ren XR, Chen W, Castro H, Lehmann F, Spector N et al. Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected]. J Transl Med 2012; 10:28; PMID:22325452; http://dx.doi.org/10.1186/1479-5876-10-28
  • Ren XR, Wei J, Lei G, Wang J, Lu J, Xia W, Spector N, Barak LS, Clay TM, Osada T et al. Polyclonal HER2-specific antibodies induced by vaccination mediate receptor internalization and degradation in tumor cells. Breast Cancer Res 2012; 14:R89; PMID:22676470; http://dx.doi.org/10.1186/bcr3204
  • Allen CD, Okada T, Tang HL, Cyster JG. Imaging of germinal center selection events during affinity maturation. Science 2007; 315:528-31; PMID:17185562; http://dx.doi.org/10.1126/science.1136736
  • Savelyeva N, King CA, Vitetta ES, Stevenson FK. Inhibition of a vaccine-induced anti-tumor B cell response by soluble protein antigen in the absence of continuing T cell help. Proc Natl Acad Sci U S A 2005; 102:10987-92; PMID:16037207; http://dx.doi.org/10.1073/pnas.0505108102
  • Savelyeva N, Shipton M, Suchacki A, Babbage G, Stevenson FK. High-affinity memory B cells induced by conjugate vaccines against weak tumor antigens are vulnerable to nonconjugated antigen. Blood 2011; 118:650-9; PMID:21613251; http://dx.doi.org/10.1182/blood-2011-01-328864
  • Nurieva RI, Liu X, Dong C. Molecular mechanisms of T-cell tolerance. Immunol Rev 2011; 241:133-44; PMID:21488895; http://dx.doi.org/10.1111/j.1600-065X.2011.01012.x
  • King CA, Spellerberg MB, Zhu D, Rice J, Sahota SS, Thompsett AR, Hamblin TJ, Radl J, Stevenson FK. DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma. Nat Med 1998; 4:1281-6; PMID:9809552; http://dx.doi.org/10.1038/3266
  • Stevenson FK, Ottensmeier CH, Johnson P, Zhu D, Buchan SL, McCann KJ, Roddick JS, King AT, McNicholl F, Savelyeva N et al. DNA vaccines to attack cancer. Proc Natl Acad Sci U S A 2004; 101 Suppl 2:14646-52; PMID:15292504; http://dx.doi.org/10.1073/pnas.0404896101
  • McCann KJ, Godeseth R, Chudley L, Mander A, Di Genova G, Lloyd-Evans P, Kerr JP, Malykh VB, Jenner MW, Orchard KH et al. Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study. Cancer Immunol Immunother 2015; 64:1021-32; PMID:25982371; http://dx.doi.org/10.1007/s00262-015-1703-7
  • Chudley L, McCann K, Mander A, Tjelle T, Campos-Perez J, Godeseth R, Creak A, Dobbyn J, Johnson B, Bass P et al. DNA fusion-gene vaccination in patients with prostate cancer induces high-frequency CD8(+) T-cell responses and increases PSA doubling time. Cancer Immunol Immunother 2012; 61:2161-70; PMID:22729556; http://dx.doi.org/10.1007/s00262-012-1270-0
  • Campos-Perez J, Rice J, Escors D, Collins M, Paterson A, Savelyeva N, Stevenson FK. DNA fusion vaccine designs to induce tumor-lytic CD8+ T-cell attack via the immunodominant cysteine-containing epitope of NY-ESO 1. Int J Cancer 2013; 133:1400-7; PMID:23494538; http://dx.doi.org/10.1002/ijc.28156
  • Gleba Y, Klimyuk V, Marillonnet S. Viral vectors for the expression of proteins in plants. Curr Opin Biotechnol 2007; 18:134-41; PMID:17368018; http://dx.doi.org/10.1016/j.copbio.2007.03.002
  • Gleba Y, Klimyuk V, Marillonnet S. Magnifection–a new platform for expressing recombinant vaccines in plants. Vaccine 2005; 23:2042-8; PMID:15755568; http://dx.doi.org/10.1016/j.vaccine.2005.01.006
  • Klimyuk V, Pogue G, Herz S, Butler J, Haydon H. Production of recombinant antigens and antibodies in Nicotiana benthamiana using ‘magnifection’ technology: GMP-compliant facilities for small- and large-scale manufacturing. Curr Top Microbiol Immunol 2014; 375:127-54; PMID:22527176; http://dx.doi.org/10.1007/82_2012_212
  • MacLeod MK, McKee AS, David A, Wang J, Mason R, Kappler JW, Marrack P. Vaccine adjuvants aluminum and monophosphoryl lipid A provide distinct signals to generate protective cytotoxic memory CD8 T cells. Proc Natl Acad Sci U S A 2011; 108:7914-9; PMID:21518876; http://dx.doi.org/10.1073/pnas.1104588108
  • Garulli B, Stillitano MG, Barnaba V, Castrucci MR. Primary CD8+ T-cell response to soluble ovalbumin is improved by chloroquine treatment in vivo. Clin Vaccine Immunol 2008; 15:1497-504; PMID:18753338; http://dx.doi.org/10.1128/CVI.00166-08
  • Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW, Jr, Leahy DJ. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003; 421:756-60; PMID:12610629; http://dx.doi.org/10.1038/nature01392
  • Rolla S, Marchini C, Malinarich S, Quaglino E, Lanzardo S, Montani M, Iezzi M, Angeletti M, Ramadori G, Forni G et al. Protective immunity against neu-positive carcinomas elicited by electroporation of plasmids encoding decreasing fragments of rat neu extracellular domain. Hum Gene Ther 2008; 19:229-40; PMID:18269312; http://dx.doi.org/10.1089/hum.2006.196
  • Quaglino E, Mastini C, Forni G, Cavallo F. ErbB2 transgenic mice: a tool for investigation of the immune prevention and treatment of mammary carcinomas. Curr Protoc Immunol 2008; 20 9:1-9-10; PMID:18729063; http://dx.doi.org/10.1002/0471142735.im2009s82
  • Piechocki MP, Pilon SA, Wei WZ. Complementary antitumor immunity induced by plasmid DNA encoding secreted and cytoplasmic human ErbB-2. J Immunol 2001; 167:3367-74; PMID:11544327; http://dx.doi.org/10.4049/jimmunol.167.6.3367
  • Quaglino E, Iezzi M, Mastini C, Amici A, Pericle F, Di Carlo E, Pupa SM, De Giovanni C, Spadaro M, Curcio C et al. Electroporated DNA vaccine clears away multifocal mammary carcinomas in her-2/neu transgenic mice. Cancer Res 2004; 64:2858-64; PMID:15087404; http://dx.doi.org/10.1158/0008-5472.CAN-03-2962
  • Husemann Y, Geigl JB, Schubert F, Musiani P, Meyer M, Burghart E, Forni G, Eils R, Fehm T, Riethmuller G et al. Systemic spread is an early step in breast cancer. Cancer Cell 2008; 13:58-68; PMID:18167340; http://dx.doi.org/10.1016/j.ccr.2007.12.003
  • Rolla S, Ria F, Occhipinti S, Di Sante G, Iezzi M, Spadaro M, Nicolo C, Ambrosino E, Merighi IF, Musiani P et al. Erbb2 DNA vaccine combined with regulatory T cell deletion enhances antibody response and reveals latent low-avidity T cells: potential and limits of its therapeutic efficacy. J Immunol 2010; 184:6124-32; PMID:20435927; http://dx.doi.org/10.4049/jimmunol.0901215
  • Reinhardt RL, Liang HE, Locksley RM. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 2009; 10:385-93; PMID:19252490; http://dx.doi.org/10.1038/ni.1715
  • Pullen GR, Fitzgerald MG, Hosking CS. Antibody avidity determination by ELISA using thiocyanate elution. J Immunol Methods 1986; 86:83-7; PMID:3944471; http://dx.doi.org/10.1016/0022-1759(86)90268-1
  • Einstein MH, Baron M, Levin MJ, Chatterjee A, Edwards RP, Zepp F, Carletti I, Dessy FJ, Trofa AF, Schuind A et al. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years. Hum Vaccin 2009; 5:705-19; PMID:19684472; http://dx.doi.org/10.4161/hv.5.10.9518
  • Riccardo F, Bolli E, Macagno M, Arigoni M, Cavallo F, Quaglino E. Chimeric DNA Vaccines: An Effective Way to Overcome Immune Tolerance. Curr Top Microbiol Immunol 2014; PMID:25294003
  • Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 2004; 5:317-28; PMID:15093539; http://dx.doi.org/10.1016/S1535-6108(04)00083-2
  • Tuse D, Tu T, McDonald KA. Manufacturing economics of plant-made biologics: case studies in therapeutic and industrial enzymes. Biomed Res Int 2014; 2014:256135; PMID:24977145; http://dx.doi.org/10.1155/2014/256135
  • Matic S, Quaglino E, Arata L, Riccardo F, Pegoraro M, Vallino M, Cavallo F, Noris E. The rat ErbB2 tyrosine kinase receptor produced in plants is immunogenic in mice and confers protective immunity against ErbB2 mammary cancer. Plant Biotechnol J 2015; 14(1):153-9; PMID:25865255; http://dx.doi.org/10.1111/pbi.12367
  • Tuse D, Ku N, Bendandi M, Becerra C, Collins R, Langford N, Sancho SI, de Cerio AL-D, Pastor F, Kandzia R et al. Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma. Bio Med Res Int 2015; 2015:648143; PMID:26425548; http://dx.doi.org/10.1155/2015/648143
  • Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 2014; 514:47-53; PMID:25171469; http://dx.doi.org/10.1038/nature13777
  • Perik PJ, de Korte MA, van Veldhuisen DJ, Gietema JA, Sleijfer DT, de Vries EG. Cardiotoxicity associated with the use of trastuzumab in breast cancer patients. Expert Rev Anticancer Ther 2007; 7:1763-71; PMID:18062750; http://dx.doi.org/10.1586/14737140.7.12.1763
  • de Korte MA, de Vries EG, Lub-de Hooge MN, Jager PL, Gietema JA, van der Graaf WT, Sluiter WJ, van Veldhuisen DJ, Suter TM, Sleijfer DT et al. 111Indium-trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: a clue to uncover the mechanisms of trastuzumab-related cardiotoxicity. Eur J Cancer 2007; 43:2046-51; PMID:17719768; http://dx.doi.org/10.1016/j.ejca.2007.06.024
  • Swain SM, Ewer MS, Cortes J, Amadori D, Miles D, Knott A, Clark E, Benyunes MC, Ross G, Baselga J. Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: a randomized, double-blind, placebo-controlled phase III study. Oncologist 2013; 18:257-64; PMID:23475636; http://dx.doi.org/10.1634/theoncologist.2012-0448
  • Quaglino E, Rolla S, Iezzi M, Spadaro M, Musiani P, De Giovanni C, Lollini PL, Lanzardo S, Forni G, Sanges R et al. Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions. J Clin Invest 2004; 113:709-17; PMID:14991069; http://dx.doi.org/10.1172/JCI19850
  • Nanni P, Landuzzi L, Nicoletti G, Giovanni C, Rossi I, Croci S, Astolfi A, Iezzi M, Di Carlo E, Musiani P et al. Immunoprevention of mammary carcinoma in HER-2/neu transgenic mice is IFN-gamma and B cell dependent. J Immunol 2004; 173:2288-96; PMID:15294941; http://dx.doi.org/10.4049/jimmunol.173.4.2288
  • Goodnow CC, Crosbie J, Adelstein S, Lavoie TB, Smith-Gill SJ, Brink RA, Pritchard-Briscoe H, Wotherspoon JS, Loblay RH, Raphael K et al. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 1988; 334:676-82; PMID:3261841; http://dx.doi.org/10.1038/334676a0
  • MacLennan IC, Toellner KM, Cunningham AF, Serre K, Sze DM, Zuniga E, Cook MC, Vinuesa CG. Extrafollicular antibody responses. Immunol Rev 2003; 194:8-18; PMID:12846803; http://dx.doi.org/10.1034/j.1600-065X.2003.00058.x
  • Mukhopadhyay A, Dyring C, Stott DI. Comparison of prophylactic and therapeutic immunisation with an ErbB-2 (HER2) fusion protein and immunoglobulin V-gene repertoire analysis in a transgenic mouse model of spontaneous breast cancer. Vaccine 2014; 32:1012-8; PMID:24231440; http://dx.doi.org/10.1016/j.vaccine.2013.10.077
  • Stevenson FK, Palucka K. Understanding and activating immunity against human cancer. Curr Opin Immunol 2010; 22:212-4; PMID:20338741; http://dx.doi.org/10.1016/j.coi.2010.03.001
  • Coussens L, Yangfeng TL, Liao YC, Chen E, Gray A, Mcgrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U et al. Tyrosine Kinase Receptor with Extensive Homology to Egf Receptor Shares Chromosomal Location with Neu Oncogene. Science 1985; 230:1132-9; PMID:2999974; http://dx.doi.org/10.1126/science.2999974
  • Rovero S, Amici A, Di Carlo E, Bei R, Nanni P, Quaglino E, Porcedda P, Boggio K, Smorlesi A, Lollini PL et al. DNA vaccination against rat her-2/Neu p185 more effectively inhibits carcinogenesis than transplantable carcinomas in transgenic BALB/c mice. J Immunol 2000; 165:5133-42; PMID:11046045; http://dx.doi.org/10.4049/jimmunol.165.9.5133
  • Di Genova G, Savelyeva N, Suchacki A, Thirdborough SM, Stevenson FK. Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid. Eur J Immunol 2010; 40:976-85; PMID:20104490; http://dx.doi.org/10.1002/eji.200940017
  • McCann KJ, Mander A, Cazaly A, Chudley L, Stasakova J, Thirdborough SM, King A, Lloyd-Evans P, Buxton E, Edwards C, Halford S, Bateman A, O'Callaghan A, Clive S, Anthoney A, Jodrell DI, Weinschenk T, Simon P, Sahin U, Thomas GJ, Stevenson FK, Ottensmeier CH. Targeting Carcinoembryonic Antigen with DNA Vaccination: On-Target Adverse Events Link with Immunological and Clinical Outcomes. Clin Cancer Res. 2016. pii: clincanres.2507.2015. [Epub ahead of print]; PMID:27091407; http://www.ncbi.nlm.nih.gov/pubmed/27091407