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. 2018 Sep 10;9(9):CD007287.
doi: 10.1002/14651858.CD007287.pub4.

Antigen-specific active immunotherapy for ovarian cancer

Sterre T Paijens  1 , Ninke Leffers, Toos Daemen, Wijnand Helfrich, H Marike Boezen, Ben J Cohlen, Cornelis Jm Melief, Marco de Bruyn, Hans W Nijman
Affiliations

Antigen-specific active immunotherapy for ovarian cancer

Sterre T Paijens et al. Cochrane Database Syst Rev. .

Abstract

Background: This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer.

Objectives: Primary objective• To assess the clinical efficacy of antigen-specific active immunotherapy for the treatment of ovarian cancer as evaluated by tumour response measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival differences◦ In addition, we recorded the numbers of observed antigen-specific humoral and cellular responsesSecondary objective• To establish which combinations of immunotherapeutic strategies with tumour antigens provide the best immunological and clinical results SEARCH METHODS: For the previous version of this review, we performed a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase databases, and clinicaltrials.gov (1966 to July 2009). We also conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For the first update of this review, we extended the searches to October 2013, and for this update, we extended the searches to July 2017.

Selection criteria: We searched for randomised controlled trials (RCTs), as well as non-randomised studies (NRSs), that included participants with epithelial ovarian cancer, irrespective of disease stage, who were treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, treatment schedule, and reported clinical or immunological outcomes.

Data collection and analysis: Two reviews authors independently extracted the data. We evaluated the risk of bias for RCTs according to standard methodological procedures expected by Cochrane, and for NRSs by using a selection of quality domains deemed best applicable to the NRS.

Main results: We included 67 studies (representing 3632 women with epithelial ovarian cancer). The most striking observations of this review address the lack of uniformity in conduct and reporting of early-phase immunotherapy studies. Response definitions show substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events is frequently limited. Furthermore, reports of both RCTs and NRSs frequently lack the relevant information necessary for risk of bias assessment. Therefore, we cannot rule out serious biases in most of the included trials. However, selection, attrition, and selective reporting biases are likely to have affected the studies included in this review. GRADE ratings were high only for survival; for other primary outcomes, GRADE ratings were very low.The largest body of evidence is currently available for CA-125-targeted antibody therapy (17 studies, 2347 participants; very low-certainty evidence). Non-randomised studies of CA-125-targeted antibody therapy suggest improved survival among humoral and/or cellular responders, with only moderate adverse events. However, four large randomised placebo-controlled trials did not show any clinical benefit, despite induction of immune responses in approximately 60% of participants. Time to relapse with CA-125 monoclonal antibody versus placebo, respectively, ranged from 10.3 to 18.9 months versus 10.3 to 13 months (six RCTs, 1882 participants; high-certainty evidence). Only one RCT provided data on overall survival, reporting rates of 80% in both treatment and placebo groups (three RCTs, 1062 participants; high-certainty evidence). Other small studies targeting many different tumour antigens have presented promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results and the limited side effects and toxicity reported, exploration of clinical efficacy in large well-designed RCTs may be worthwhile.

Authors' conclusions: We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously, as review authors found a significant dearth of relevant information for assessment of risk of bias in both RCTs and NRSs.

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Conflict of interest statement

Ninke Leffers, Cornelis Melief, Toos Daemen, and Hans Nijman were investigators in two studies included in this review (Leffers 2009a; Vermeij 2012). No potential conflicts of interest are known for the other contributing review authors (WH, BJC, STP, MDB) .

Figures

1
1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. The high risk of selection bias in the majority of included studies is a reflection of the large number of uncontrolled studies included in this review. The risk of remaining biases could not be adequately judged for the included uncontrolled studies, thus explaining the large percentage of missing risk assessments.
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    1. Takeoka T, Nagase H, Kurose K, Ohue Y, Yamasaki M, Takiguchi S, et al. NY‐ESO‐1 protein cancer vaccine with Poly‐ICLC and OK‐432: rapid and strong induction of NY‐ESO‐1‐specific immune responses by Poly‐ICLC. Journal of Immunotherapy 2017;40:140‐7. [PUBMED: 28338507] - PubMed
Takeuchi 2013 {published data only}
    1. Takeuchi S, Shoji T, Kagabu M, Honda T, Miura F, Omi H, et al. A phase I/II study of multiple peptides cocktail vaccine for advanced/recurrent ovarian cancer. American Society of Clinical Oncology Annual Meeting. 2013.
Tsuda 2004 {published data only}
    1. Tsuda N, Mochizuki K, Harada M, Sukehiro A, Kawano K, Yamada A, et al. Vaccination with predesignated or evidence‐based peptides for patients with recurrent gynecologic cancers. Journal of Immunotherapy 2004;27(1):60‐72. - PubMed
van Zanten‐Przybysz 2002 {published data only}
    1. Zanten‐Przybysz I, Molthoff C, Gebbinck JK, Mensdorff‐Pouilly S, Verstraeten R, Kenemans P, et al. Cellular and humoral responses after multiple injections of unconjugated chimeric monoclonal antibody MOv18 in ovarian cancer patients: a pilot study. Journal of Cancer Research and Clinical Oncology 2002;128(9):484‐92. - PubMed
Vermeij 2012 {published data only}
    1. Vermeij R, Leffers N, Hoogeboom BN, Hamming LE, Wolf R, Reyners AKL, et al. Potentiation of a p53‐SLP vaccine by cyclophosphamide in ovarian cancer: a single‐arm phase II study. International Journal of Cancer 2012;131:E670‐80. - PubMed
Wagner 1993 {published data only}
    1. Wagner U. Antitumor antibodies for immunotherapy of ovarian carcinomas. Hybridoma 1993;12(5):521‐8. - PubMed
    1. Wagner U, Reinsberg J, Schmidt S, Mallmann P, Schmolling J, Schultes B, et al. Monoclonal antibodies and idiotypic network activation for ovarian carcinoma. Cell Biophysics 1994;24‐25:237‐42. - PubMed

References to studies excluded from this review

Anderson 2000 {published data only}
    1. Anderson BW, Kudelka AP, Honda T, Pollack MS, Gershenson DM, Gillogly MA, et al. Induction of determinant spreading and of Th1 responses by in vitro stimulation with HER‐2 peptides. Cancer Immunology, Immunotherapy 2000;49(9):459‐68. - PMC - PubMed
Baek 2015 {published data only}
    1. Baek S, Kim YM, Kim SB, Kim CS, Kwon SW, Kim Y. Therapeutic DC vaccination with IL‐2 as a consolidation therapy for ovarian cancer patients: a phase I/II trial. Cellular & Molecular Immunology 2015;12:87‐95. [PUBMED: 24976269] - PMC - PubMed
Bapsy 2014 {published data only}
    1. Bapsy PP, Sharan B, Kumar C, Das RP, Rangarajan B, Jain M. Open‐label, multi‐center, non‐randomized, single‐arm study to evaluate the safety and efficacy of dendritic cell immunotherapy in patients with refractory solid malignancies, on supportive care. Cytotherapy 2014;16(2):234‐44. [PUBMED: 24438902] - PubMed
Bender 2007 {published data only}
    1. Bender A, Karbach J, Neumann A, Jager D, Al‐Batran SE, Atmaca A, et al. LUD 00‐009: phase 1 study of intensive course immunization with NY‐ESO‐1 peptides in HLA‐A2 positive patients with NY‐ESO‐1‐expressing cancer. Cancer Immunology, Immunotherapy 2007;7:16. - PMC - PubMed
Bernal 2012 {published data only}
    1. Bernal SD, Ona ET, Riego‐Javier E, Villa R, Cristal‐Luna GR, Laguatan JB, et al. Anticancer immune reactivity and long‐term survival after treatment of metastatic ovarian cancer with dendritic cells. Oncology Letters 2012;3:66‐74. - PMC - PubMed
Carbone 2005 {published data only}
    1. Carbone DP, Ciernik IF, Kelley MJ, Smith MC, Nadaf S, Kavanaugh D, et al. Immunization with mutant p53‐ and K‐ras‐derived peptides in cancer patients: immune response and clinical outcome. Journal of Clinical Oncology 2005;23(22):5099‐107. - PubMed
Chiang 2013 {published data only}
    1. Chiang CL, Kandalaft LE, Tanyi J, Hagemann AR, Motz GT, Svoronos N. A dendritic cell vaccine pulsed with autologous hypochlorous acid‐oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside. Clinical Cancer Research 2013;19(17):4801‐15. [PUBMED: 23838316] - PMC - PubMed
Coosemans 2013 {published data only}
    1. Coosemans A, Vanderstraeten A, Tuyaerts S, Verschuere T, Moerman P, Berneman Z. Immunological response after WT1 mRNA‐loaded dendritic cell immunotherapy in ovarian carcinoma and carcinosarcoma. Anticancer Research 2013;33(9):3855‐9. [PUBMED: 24023319] - PubMed
Dhodapkar 2014 {published data only}
    1. Dhodapkar MV, Sznol M, Zhao B, Wang D, Carvajal RD, Keohan ML, et al. Induction of antigen‐specific immunity with a vaccine targeting NY‐ESO‐1 to the dendritic cell receptor DEC‐205. Science Translational Medicine 2014;6(232):51. [PUBMED: 24739759] - PMC - PubMed
Disis 1999 {published data only}
    1. 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. Clinical Cancer Research 1999;5(6):1289‐97. - PubMed
Disis 2000 {published data only}
    1. Disis ML, Schiffman K, Gooley TA, McNeel DG, Rinn K, Knutson KL. Delayed‐type hypersensitivity response is a predictor of peripheral blood T‐cell immunity after HER‐2/neu peptide immunization. Clinical Cancer Research 2000;6(4):1347‐50. - PubMed
Disis 2002 {published data only}
    1. Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, et al. Generation of T‐cell immunity to the HER‐2/neu protein after active immunization with HER‐2/neu peptide‐based vaccines. Journal of Clinical Oncology 2002;20(11):2624‐32. - PubMed
Disis 2002a {published data only}
    1. Disis ML, Rinn K, Knutson KL, Davis D, Caron D, dela Rosa C, et al. Flt3 ligand as a vaccine adjuvant in association with HER‐2/neu peptide‐based vaccines in patients with HER‐2/neu‐overexpressing cancers. Blood 2002;99(8):2845‐50. - PubMed
Disis 2004 {published data only}
    1. Disis ML, Goodell V, Schiffman K, Knutson KL. Humoral epitope‐spreading following immunization with a HER‐2/neu peptide based vaccine in cancer patients. Journal of Clinical Immunology 2004;24(5):571‐8. - PubMed
Disis 2004a {published data only}
    1. Disis ML, Schiffman K, Guthrie K, Salazar LG, Knutson KL, Goodell V, et al. Effect of dose on immune response in patients vaccinated with an her‐2/neu intracellular domain protein‐‐based vaccine. Journal of Clinical Oncology 2004;22(10):1916‐25. - PubMed
Galanis 2013 {published data only}
    1. Galanis E, Atherton P, Dowdy S, Cliby W, Haluska P, Long H, et al. Intraperitoneal (IP) administration of an oncolytic measles virus (MV) strain expressing the sodium iodine symporter gene in patients (pts) with advanced ovarian cancer (ovca). American Society of Gene & Cell Therapy (ASGCT) Annual Meeting. 2013.
Haakenstad 2012 {published data only}
    1. Haakenstad H, Suso EMI, Rasmussen AM, Larsen SS, Dueland S, Lilleby W, et al. Clinical use of fast DCs transfected with hTERT and Survivin mRNA ‐ an effective and simplified cancer vaccine approach. European Group for Blood and Marrow Transplantation Annual Meeting. 2012.
    1. Kvalheim G, Suso E, Rasmussen A, Honnashagen T, Dueland S, Gaudernack G. Fast DCs transfected with hTERT and Survivin mRNA ‐ a novel, effective and simplified cancer vaccine approach. European Group for Blood and Marrow Transplantation Annual Meeting. 2011.
Hasumi 2011 {published data only}
    1. Hasumi K, Aoki Y, Watanabe R, Hankey KG, Mann DL. Therapeutic response in patients with advanced malignancies treated with combined dendritic cell‐activated T cell based immunotherapy and intensity‐modulated radiotherapy. Cancers 2011;3:2223‐42. - PMC - PubMed
Hernando 2002 {published data only}
    1. Hernando JJ, Park TW, Kubler K, Offergeld R, Schlebusch H, Bauknecht T. Vaccination with autologous tumour antigen‐pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial. Cancer Immunology, Immunotherapy 2002;51(1):45‐52. - PMC - PubMed
Hernando 2007 {published data only}
    1. Hernando JJ, Park T‐W, Fischer H‐P, Zivanovic O, Braun M, Polcher M, et al. Vaccination with dendritic cells transfected with mRNA‐encoded folate‐receptor‐(alpha) for relapsed metastatic ovarian cancer. Lancet Oncology 2007;8(5):451‐4. - PubMed
Holmberg 2000 {published data only}
    1. Holmberg LA, Oparin DV, Gooley T, Lilleby K, Bensinger W, Reddish MA, et al. Clinical outcome of breast and ovarian cancer patients treated with high‐dose chemotherapy, autologous stem cell rescue and THERATOPE STn‐KLH cancer vaccine. Bone Marrow Transplant 2000;25(12):1233‐41. - PubMed
Hui 1997 {published data only}
    1. Hui KM, Ang PT, Huang L, Tay SK. Phase I study of immunotherapy of cutaneous metastases of human carcinoma using allogeneic and xenogeneic MHC DNA‐liposome complexes. Gene Therapy 1997;4(8):783‐90. - PubMed
Jackson 2017 {published data only}
    1. Jackson D, Byrd K, Vreeland T, Hale D, Herbert G, Greene JM, et al. Interim analysis of a phase I/IIa trial assessing E39+GM‐CSF, a folate binding protein vaccine, to prevent recurrence in ovarian and endometrial cancer patients. Oncotarget 2017;8:15912‐23. - PMC - PubMed
Jager 2006 {published data only}
    1. Jager E, Karbach J, Gnjatic S, Neumann A, Bender A, Valmori D, et al. Recombinant vaccinia/fowlpox NY‐ESO‐1 vaccines induce both humoral and cellular NY‐ESO‐1‐specific immune responses in cancer patients. Proceedings of the National Academy of Sciences of the United States of America 2006;103(39):14453‐8. - PMC - PubMed
Kandalaft 2010 {published data only}
    1. Coukos G, Powell D, Kandalaft L, Smith L, Chu C, Rubin S, et al. Autologous whole‐tumor antigen combinatorial immunotherapy for recurrent ovarian cancer. Gynecologic Oncology 2010;116:s130.
    1. Kandalaft LE, Powell DJ, Smith L, Adams S, Liao J, Hageman A, et al. Autologous whole‐tumor anitgen combinatorial immunotherapy for recurrent ovarian cancer. Journal of Immunotherapy 2010;33(8):878.
Karbach 2010 {published data only}
    1. Karbach J, Gnjatic S, Bender A, Neumann A, Weidmann E, Yuan J, et al. Tumor‐reactive CD8+ T‐cell responses after vaccination with NY‐ESO‐1 peptide, CpG 7909 and Montanide ISA‐51: association with survival. International Journal of Cancer 2010;126:909‐18. - PubMed
Kato 2010 {published data only}
    1. Kato Y. WT1 peptide pulsed dendritic cell therapy with activated T lymphocytes therapy for advanced cancers. Gan To Kagaku Ryoho 2010;37(12):2240‐2. - PubMed
Khranovska 2011 {published data only}
    1. Khranovska NM, Svyntsytsky VS, Potebnya GP, Vorobyova LI, Skachkova OV, Tsyp NP, et al. New dendritic cell vaccine therapy approach ‐ randomized phase I/II study in III‐IV stage ovarian cancer patients. European Multidisciplinary Cancer Conference (ECCO ESMO ESTRO). 2011.
Knutson 2001 {published data only}
    1. Knutson KL, Schiffman K, Disis ML. Immunization with a HER‐2/neu helper peptide vaccine generates HER‐2/neu CD8 T‐cell immunity in cancer patients. Journal of Clinical Investigation 2001;107(4):477‐84. - PMC - PubMed
Knutson 2002 {published data only}
    1. 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 peptide‐specific immunity. Clinical Cancer Research 2002;8(5):1014‐8. - PubMed
Letsch 2008 {published data only}
    1. Letsch A, Asemissen AM, Zimmermann K, Bauer S, Stather D, Völker‐Call M, et al. Different quality of T cell responses to WT1 peptide vaccination in patients with AML/MDS and patients with solid tumors. Journal of Immunotherapy. 2008; Vol. 31:943‐4.
Loveland 2006 {published data only}
    1. Loveland BE, Zhao A, White S, Gan H, Hamilton K, Xing PX, et al. Mannan‐MUC1‐pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma. Clinical Cancer Research 2006;12(3 Pt 1):869‐77. - PubMed
Manjunath 2012 {published data only}
    1. Manjunath SR, Ramanan G, Dedeepiya VD, Terunuma H, Deng X, Baskar S, et al. Autologous immune enhancement therapy in recurrent ovarian cancer with metastases: a case report. Case Reports in Oncology 2012;5:114‐8. - PMC - PubMed
Marshall 2005 {published data only}
    1. Marshall JL, Gulley JL, Arlen PM, Beetham PK, Tsang KY, Slack R, et al. Phase I study of sequential vaccinations with fowlpox‐CEA(6D)‐TRICOM alone and sequentially with vaccinia‐CEA(6D)‐TRICOM, with and without granulocyte‐macrophage colony‐stimulating factor, in patients with carcinoembryonic antigen‐expressing carcinomas. Journal of Clinical Oncology 2005;23:720‐31. - PubMed
Matsuzaki 2014 {published data only}
    1. Matsuzaki J, Tsuji T, Luescher I, Old LJ, Shrikant P, Gnjatic S. Nonclassical antigen‐processing pathways are required for MHC class II‐restricted direct tumor recognition by NY‐ESO‐1‐specific CD4(+) T cells. Cancer Immunology Research 2014;2(4):341‐50. [PUBMED: 24764581] - PMC - PubMed
Miotti 1999 {published data only}
    1. Miotti S, Negri DR, Valota O, Calabrese M, Bolhuis RL, Gratama JW, et al. Level of anti‐mouse‐antibody response induced by bi‐specific monoclonal antibody OC/TR in ovarian‐carcinoma patients is associated with longer survival. International Journal of Cancer 1999;84(1):62‐8. - PubMed
Morera 2017 {published data only}
    1. Morera Y, Sánchez J, Bequet‐Romero M, Selman‐Housein KH, Torre A, Hernández‐Bernal F. Specific humoral and cellular immune responses in cancer patients undergoing chronic immunization with a VEGF‐based therapeutic vaccine. Vaccine 2017;35:3582‐90. [PUBMED: 28536029] - PubMed
Morse 1999 {published data only}
    1. Morse MA, Deng Y, Coleman D, Hull S, Kitrell‐Fisher E, Nair S, et al. A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP‐1)‐pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clinical Cancer Research 1999;5(6):1331‐8. - PubMed
Morse 2003 {published data only}
    1. Morse MA, Clay TM, Colling K, Hobeika A, Grabstein K, Cheever MA, et al. Her2 dendritic cell vaccines. Clinical Breast Cancer 2003;3(Suppl 4):S164‐72. - PubMed
Morse 2011a {published data only}
    1. Morse MA, Chapman R, Powerdly J, Blackwell K, Keler T, Green J, et al. Phase I study utilizing a novel antigen‐presenting cell‐targeted vaccine with toll‐like receptor stimulation to induce immunity to self‐antigens in cancer patients. Clinical Cancer Research 2011;17(14):4844‐53. - PMC - PubMed
Murray 2002 {published data only}
    1. Murray JL, Gillogly ME, Przepiorka D, Brewer H, Ibrahim NK, Booser DJ, et al. Toxicity, immunogenicity, and induction of E75‐specific tumor‐lytic 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. Clinical Cancer Research 2002;8(11):3407‐18. - PubMed
Oh 2016 {published data only}
    1. Oh J, Barve M, Matthews CM, Koon EC, Heffernan TP, Fine B. Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer. Gynaecologic Oncology 2016;143(3):504‐10. [27678295] - PubMed
Parkhurst 2004 {published data only}
    1. Parkhurst MR, Riley JP, Igarashi T, Li Y, Robbins PF, Rosenberg SA. Immunization of patients with the hTERT:540‐548 peptide induces peptide‐reactive T lymphocytes that do not recognize tumors endogenously expressing telomerase. Clinical Cancer Research 2004;10(14):4688‐98. - PMC - PubMed
Reddish 1996 {published data only}
    1. Reddish MA, MacLean GD, Poppema S, Berg A, Longenecker BM. Pre‐immunotherapy serum CA27.29 (MUC‐1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl‐Tn‐KLH cancer vaccine in active specific immunotherapy. Cancer Immunology, Immunotherapy 1996;42(5):303‐9. - PMC - PubMed
Salazar 2006 {published data only}
    1. Salazar LG, Murray JL, Disis ML, Cheever M. A phase I vaccine trial of a HER‐2/neu peptide incorporated into PLG microspheres in patients with advanced stage HER2‐expressing cancers. ASCO Annual Meeting. 2006.
Schiffman 2002 {published data only}
    1. Schiffman K, Rinn K, Disis ML. Delayed type hypersensitivity response to recall antigens does not accurately reflect immune competence in advanced stage breast cancer patients. Breast Cancer Research and Treatment 2002;74(1):17‐23. - PubMed
Tsuji 2013 {published data only}
    1. Tsuji T, Sabbatini P, Jungbluth AA, Ritter E, Pan L, Ritter G, et al. Effect of Montanide and poly‐ICLC adjuvant on human self/tumor antigen‐specific CD4+ T cells in phase I overlapping long peptide vaccine trial. Cancer Immunology Research 2013;1:340‐50. [DOI: 10.1158/2326-6066.CIR-13-0089] - DOI - PubMed
Yacyshyn 1995 {published data only}
    1. Yacyshyn MB, Poppema S, Berg A, MacLean GD, Reddish MA, Meikle A, et al. CD69+ and HLA‐DR+ activation antigens on peripheral blood lymphocyte populations in metastatic breast and ovarian cancer patients: correlations with survival following active specific immunotherapy. International Journal of Cancer 1995;61(4):470‐4. - PubMed
Zaks 1998 {published data only}
    1. 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 Research 1998;58(21):4902‐8. - PubMed

References to ongoing studies

NCT00003002 {unpublished data only}
    1. University of Washington. Her‐2/Neu vaccine plus GM‐CSF in treating patients with stage III or stage IV breast, ovarian, or non‐small cell lung cancer. clinicaltrials.gov.
NCT00004604 {unpublished data only}
    1. Duke University. Biological therapy in treating patients with metastatic cancer. clinicaltrials.gov.
NCT00006041 {unpublished data only}
    1. Memorial Sloan ‐ Kettering Cancer Center. Vaccine therapy in treating patients with ovarian, fallopian tube, or peritoneal cancer. clinicaltrials.gov.
NCT00381173 {unpublished data only}
    1. Eisai Medical Research Inc. A phase 1 open‐label study of the safety and feasibility of ZYC300 administration with cyclophosphamide pre‐dosing. clinicaltrials.gov.
NCT00803569 {unpublished data only}
    1. Roswell Park Cancer Institute and National Cancer Institute (NCI). Phase I study of ALVAC(2)‐NY‐ESO‐1(M)/TRICOM in patients with epithelial ovarian, fallopian tube or primary peritoneal carcinoma whose tumors express NY‐ESO‐1 or LAGE‐1 antigen. clinicaltrilas.gov.
NCT01223235 {unpublished data only}
    1. Memorial Sloan ‐ Kettering Cancer Center. Polyvalent vaccine‐KLH conjugate + Opt‐821 given in combination with bevacuzimab. clinicaltrials.gov.
NCT01322802 {unpublished data only}
    1. University of Washington. Vaccine therapy in treating patients with stage III‐IV or recurrent ovarian cancer. clinicaltrials.gov.
NCT01376505 {unpublished data only}
    1. Pravin Kaumaya. Vaccine therapy in treating patients with metastatic solid tumors. clinicaltrials.gov.
NCT01522820 {unpublished data only}
    1. Roswell Park Cancer Institute. Vaccine therapy with or without sirolimus in treating patients with NY‐ESO‐1 expressing solid tumors. clinicaltrials.gov.
NCT01536054 {unpublished data only}
    1. Roswell Park Cancer Institute. Sirolimus and vaccine therapy in treating patients with stage II‐IV ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer. clinicaltrials.gov.
NCT01556841 {unpublished data only}
    1. Oxford BioMedica. The activity of TroVax versus placebo in relapsed asymptomatic ovarian cancer (TRIOC). clinicaltrials.gov.
NCT01584115 {unpublished data only}
    1. Instituto de Investigacao em Imunologia. Clinical trial of a therapeutic vaccine with NY‐ESO‐1 in combination with the adjuvant monophosphoryl lipid A (MPLA). clinicaltrials.gov.
NCT01606241 {unpublished data only}
    1. Mayo Clinic. Cyclophosphamide and vaccine therapy in treating patients with stage II‐III breast, ovarian, primary peritoneal, or fallopian tube cancer. clinicaltrials.gov.
NCT01616303 {unpublished data only}
    1. Quest PharmaTech Inc. A controlled study of the effectiveness of oregovomab (antibody) plus chemotherapy in advanced ovarian cancer. clinicaltrials.gov.
NCT01621542 {unpublished data only}
    1. Sunovion. Clinical study of WT2725 in patients with advanced solid malignancies. clinicaltrials.gov.
NCT01673217 {unpublished data only}
    1. Roswell Park Cancer Institute. Decitabine, vaccine therapy, and pegylated liposomal doxorubicin hydrochloride in treating patients with recurrent ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer. clinicaltrials.gov.
NCT02111941 {unpublished data only}
    1. Mayo Clinic. Vaccine therapy in treating patients with stage IIIC‐IV ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer following surgery and chemotherapy. clinicaltrials.gov.
NCT02132988 {unpublished data only}
    1. Mackay Memorial Hospital. Trial of active immunotherapy with Globo H‐KLH (OPT‐822/821) in women who have non‐progressive ovarian cancer. clinicaltrials.gov.
NCT02146313 {unpublished data only}
    1. Genentech, Inc. A study evaluating the safety and pharmacokinetics of DMUC4064A in participants with platinum‐resistant ovarian cancer or unresectable pancreatic cancer. clinicaltrials.gov.
NCT02166905 {unpublished data only}
    1. Roswell Park Cancer Institute. DEC‐205/NY‐ESO‐1 fusion protein CDX‐1401, Poly ICLC, and IDO1 inhibitor INCB024360 in treating patients with ovarian, fallopian tube, or primary peritoneal cancer in remission. clinicaltrials.gov.
NCT02275039 {unpublished data only}
    1. City of Hope Medical Center. P53MVA vaccine and gemcitabine hydrochloride in treating patients with recurrent ovarian epithelial cancer. clinicaltrials.gov.
NCT02387125 {unpublished data only}
    1. Immune Design. Phase 1b safety study of CMB305 in patients with locally advanced, relapsed, or metastatic cancer expressing NY‐ESO‐1. clinicaltrials.gov. - PMC - PubMed
NCT02498665 {unpublished data only}
    1. Boston Biomedical, Inc. A study of DSP‐7888 dosing emulsion in adult patients with advanced malignancies. clinicaltrials.gov.
NCT02575807 {unpublished data only}
    1. Aduro Biotech, Inc. Safety and efficacy of CRS‐207 with Epacadostat in platinum resistant ovarian, fallopian or peritoneal cancer (SEASCAPE). clinicaltrials.gov.
NCT02737787 {unpublished data only}
    1. Memorial Sloan Kettering Cancer Center. A study of WT1 vaccine and nivolumab for recurrent ovarian cancer. clinicaltrials.gov.
NCT02764333 {unpublished data only}
    1. Memorial Sloan Kettering Cancer Center. TPIV200/huFR‐1 (a multi‐epitope anti‐folate receptor vaccine) plus anti‐PD‐L1 MEDI4736 (Durvalumab) in patients with platinum resistant ovarian cancer. clinicaltrials.gov.
NCT02785250 {unpublished data only}
    1. ImmunoVaccine Technologies, Inc. Study of DPX‐Survivac vaccine therapy and Epacadostat in patients with recurrent ovarian cancer. clinicaltrials.gov.
NCT02833506 {unpublished data only}
    1. Roswell Park Cancer Institute. Sirolimus and vaccine therapy in treating patients with stage II‐IV ovarian, fallopian tube, or primary peritoneal cancer. clinicaltrials.gov.
NCT02933073 {unpublished data only}
    1. UConn Health. Study of oncoimmunome for the treatment of stage III/IV ovarian carcinoma. clinicaltrials.gov.
NCT02978222 {unpublished data only}
    1. Tapimmune Inc. Folate receptor alpha peptide vaccine with GM‐CSF versus GM‐CSF alone in patients with platinum sensitive ovarian cancer. Clinicaltrials.gov.
NCT03029403 {unpublished data only}
    1. University Health Network, Toronto. Phase 2 study of Pembrolizumab, DPX‐Survivac vaccine and Cyclophosphamide in advanced ovarian, primary peritoneal or fallopian tube cancer. clinicaltrials.gov.
NCT03029611 {unpublished data only}
    1. University of Washington. IGFBP‐2 vaccine and combination chemotherapy in treating patients with stage III‐IV ovarian, fallopian tube, or primary peritoneal cancer undergoing surgery. clinicaltrials.gov.
NCT03113487 {unpublished data only}
    1. City of Hope Medical Center. P53MVA and Pembrolizumab in treating patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. clinicaltrials.gov.
NCT03127098 {unpublished data only}
    1. NantCell, Inc. QUILT‐3.040: ETBX‐011 (Ad5 [E1‐, E2b‐]‐CEA(6D)) vaccine in combination with ALT‐803 (super‐agonist IL‐15) in subjects having CEA‐expressing cancer. clinicaltrials.gov.
NCT03197584 {unpublished data only}
    1. NantKwest, Inc. QUILT‐3.051: NANT ovarian cancer vaccine: combination immunotherapy in subjects with epithelial ovarian cancer who have progressed on or after standard‐of‐care (SOC) therapy. clinicaltrials.gov.
NCT03206047 {unpublished data only}
    1. National Cancer Institute (NCI). Atezolizumab, Guadecitabine, and CDX‐1401 vaccine in treating patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. clinicaltrials.gov.
NCT03300843 {unpublished data only}
    1. National Cancer Institute (NCI). Ability of a dendritic cell vaccine to immunize melanoma or epithelial cancer patients against defined mutated neoantigens expressed by the autologous cancer. clinicaltrials.gov.

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